Milk is one of the most complete foods, and its contamination is a serious risk to public health. Various studies on animals indicate the carcinogenicity of aflatoxin M1 (AFM1). This mycotoxin enters the milk through consumption of contaminated animal feed. The purpose of this research was to determine AFM1 in milk samples and evaluate its safety due to contamination with this mycotoxin. The samples were selected from livestock farms and transported to the laboratory under hygienic conditions. The amount of AFM1 was measured by HPLC/FLD. The extraction and clean-up stage of the samples was done using appropriate solvents and immunoaffinity columns. The reported amount was in the range of non-detected (ND) to160 ng/L. Most of the samples were lower than the permissible level of the national standard. However, in 16% of the samples, the level of AFM1 was higher than the permissible limit. Hazard Quotient (HQ) was calculated with mean data for adults and children. HQ was calculated as less than one for adults and children. Therefore, there is no noncarcinogen risk regarding the consumption of milk in terms of AFM1.

Acute kidney injury (AKI) is a significant clinical problem associated with high morbidity and mortality. Unilateral ureter obstruction (UUO) is a well-established model for studying the pathophysiology of AKI. L arginine (ARG), a precursor of nitric oxide, has been shown to possess renoprotective properties. This study aims to investigate the protective effects of ARG in an animal model of UUO-induced AKI. Male BALB/c mice were randomly allotted into sham-operated, UUO, and UUO + L-Arginine. UUO was surgically induced by ligating the left ureter. The treatment group received ARG (100, 250, and 500 mg/kg/day) intraperitoneally for seven days post-UUO surgery. Renal function was assessed by measuring plasma creatinine (Cr) and blood urea nitrogen (BUN) levels. Mitochondrial function was evaluated by determining mitochondrial membrane potential, dehydrogenases activity, and mitochondrial swelling. Oxidative stress markers, including ROS formation, lipid peroxidation, protein carbonylation, and tissue antioxidant capacity, were also measured in the kidney tissue. UUO led to significant renal dysfunction, as evidenced by increased serum Cr and BUN levels (P<0.001). Mitochondrial dysfunction was indicated by decreased mitochondrial dehydrogenase activity, mitochondrial depolarization, and increased mitochondrial swelling (P<0.001). Additionally, UUO-induced oxidative stress was demonstrated. It was found that ARG treatment significantly improved renal function by modulating mitochondrial function and decreasing oxidative stress markers (P<0.05). These findings suggest that ARG may have therapeutic potential in managing AKI by preserving mitochondrial function and reducing oxidative damage.

The numerous strategies have been conducted worldwide to mitigate the presence of these hazardous toxins. In this systematic study, these researches are summarized. The search of this study was done with keywords aflatoxin M1, AFM1, reduce, decrease, mitigation, prevent, prevention, and milk in databases without a time limit. A total of 49 manuscripts were carefully reviewed, and their data were extracted. Some interventions focused on modifying animal rations, aiming to reduce AFM1 in milk. Some were applied directly to the animals. In this method, which was done more than other research interventions, some toxin binders are used as feed additives. The third type of intervention consisted of measures that were taken directly on the milk itself. Among the three types of interventions, the use of toxin binders in animal feed was more practical and effective.

Background: Cholestasis is a multifaceted disease that influences not only the function of the liver but also affects many other organs. In this context, cholestasis-induced lung injury is a significant clinical complication. Unfortunately, there is no precise therapeutic option against cholestasis-associated lung injury. It has been revealed that oxidative stress and inflammatory response play a role in cholestasis-induced pulmonary damage. Sildenafil is a phosphodiesterase enzyme inhibitor used in the management of erectile dysfunction. Meanwhile, several experiments revealed the effects of sildenafil on oxidative stress and inflammation. This study aimed to evaluate the effect of sildenafil on cholestasis-induced oxidative stress and inflammation in cholestasis-induced lung injury. Methods: Rats underwent bile duct ligation (BDL) to induce cholestasis. Bronchoalveolar lavage fluid (BALF) levels of inflammatory cells, cytokine, and immunoglobulin were monitored at (3, 7, and 14 days after BDL surgery). Moreover, lung tissue histopathological alterations and biomarkers of oxidative stress were evaluated. Results: A significant increase in BALF inflammatory cells, TNF-α, and immunoglobulin G (IgG) was evident in BDL animals. Moreover, the infiltration of inflammatory cells, vascular congestion, and hemorrhage were detected in the lung of BDL rats. Increased markers of oxidative stress were also evident in the lung of BDL animals. Sildenafil (10 and 20 mg/kg) significantly blunted inflammatory response, oxidative stress, and histopathological alterations in the lung of cholestatic animals. Conclusion: The effects of sildenafil on inflammatory response and oxidative stress biomarkers seems to play a crucial role in its protective properties in the lung of cholestatic animals.

Ammonium ion (NH4+) is the major suspected molecule responsible for neurological complications of hepatic encephalopathy (HE). No specific pharmacological action for NH4+-induced brain injury exists so far. Excitotoxicity is a well-known phenomenon in the brain of hyperammonemic cases. The hyperactivation of the N-Methyl-d-aspartate (NMDA) receptors by agents such as glutamate, an NH4+ metabolite, could cause excitotoxicity. Excitotoxicity is connected with events such as oxidative stress and neuroinflammation. Hence, utilizing NMDA receptor antagonists could prevent neurological complications of NH4+ neurotoxicity. In the current study, C57BL6/J mice received acetaminophen (APAP; 800 mg/kg, i.p) to induce HE. Hyperammonemic animals were treated with ketamine (0.25, 0.5, and 1 mg/kg, s.c) as an NMDA receptor antagonist. Animals' brain and plasma levels of NH4+ were dramatically high, and animals' locomotor activities were disturbed. Moreover, several markers of oxidative stress were significantly increased in the brain. A significant increase in brain tissue levels of TNF-& alpha;, IL-6, and IL-1 & beta; was also detected in hyperammonemic animals. It was found that ketamine significantly normalized animals' locomotor activity, improved biomarkers of oxidative stress, and decreased proinflammatory cytokines. The effects of ketamine on oxidative stress biomarkers and inflammation seem to play a key role in its neuroprotective mechanisms in the current study.

Pesticide residues in agricultural crops, particularly vegetables, are a global concern due to their adverse impacts on human health. As spinach (Spinacia oleracea L.) is among the valuable leafy vegetables in the Iranian food basket, this survey was conducted to assess the presence of 108 pesticide residues (including organophosphorus, organochlorines, carbamates, dicarboximides, strobilurin, triazine, pyrethroids, etc.) in spinach samples, to ensure consumer safety. A total of 11 spinach samples were collected, during a ten-month period, from local markets of four different cities of Iran (Isfahan, Khash, Sari, and Karaj). Quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique was applied for sample pretreatment. Gas chromatography-mass spectrometry (GC–MS) method was applied for quantification of multi-pesticide residues in spinach samples. The obtained findings displayed that all the pesticide residues in the samples were below the LODs, and also much lower than the MRLs (maximum residue limit) set by EU/Codex. The findings showed that spinach is in a good status in terms of pesticide residues. Nevertheless, a continuous screening program is highly recommended because of the persistent nature and toxicity of applied pesticides to human health, so that any inconsistency with the maximum residues limits standards can be identified immediately and relevant actions are taken.

Cholestasis is a clinical complication that primarily influences the liver. However, it is well known that many other organs could be affected by cholestasis. Lung tissue is a major organ influenced during cholestasis. Cholestasis-induced lung injury could induce severe complications such as respiratory distress, serious pulmonary infections, and tissue fibrosis. Unfortunately, there is no specific pharmacological intervention against this complication. Several studies revealed that oxidative stress and inflammatory response play a role in cholestasis-induced lung injury. Carnosine (CARN) is a dipeptide found at high concentrations in different tissues of humans. CARN’s antioxidant and antiinflammatory properties are repeatedly mentioned in various experimental models. This study aimed to assess the role of CARN on cholestasis-induced lung injury. Rats underwent bile duct ligation (BDL) to induce cholestasis. Broncho-alveolar lavage fluid (BALF) levels of inflammatory cells, pro-inflammatory cytokines, and immunoglobulin were monitored at scheduled intervals (7, 14, and 28 days after BDL). Moreover, lung tissue histopathological alterations and biomarkers of oxidative stress were evaluated. A significant increase in BALF inflammatory cells, TNF-α, IL-1β, IL-6, and immunoglobulin-G (IgG) was detected in the BALF of BDL rats. Moreover, lung tissue histopathological changes, collagen deposition, increased TGF-β, and elevated levels of oxidative stress biomarkers were evident in cholestatic animals. It was found that CARN (100 and 500 mg/kg, i.p.) significantly alleviated lung oxidative stress biomarkers, inflammatory response, tissue fibrosis, and histopathological alterations. These data indicate the potential protective properties of CARN in the management of cholestasis-induced pulmonary damage. The effects of CARN on inflammatory response and oxidative stress biomarkers seems to play a crucial role in its protective properties in the lung of cholestatic animals.

Acute kidney injury (AKI) is an emergency condition that requires restrictive and appropriate clinical interventions. Identifying mechanisms of organ injury is a critical step in developing clinical interventions. Unilateral ureter obstruction (UUO) is widely used as an animal model for investigating AKI. The current study was designed to evaluate the role of mitochondrial impairment and oxidative stress in the pathogenesis of renal injury in UUO model. Mice underwent UUO surgery. Then, kidney tissue histopathological changes, plasma biomarkers of renal injury, oxidative stress, and different renal mitochondrial indices were evaluated at scheduled time intervals (3, 7, 14, and 21 days after UUO surgical procedure). Significant increase in plasma creatinine and blood urea nitrogen levels was evident in UUO mice. The UUO surgery induced severe kidney tissue histopathological alterations, including necrosis, severe tubular atrophy, and interstitial inflammation. Moreover, kidney biomarkers of oxidative stress included reactive oxygen species formation, lipid peroxidation, protein carbonylation, decreased glutathione reservoirs (GSH), and increased oxidized glutathione (GSSG) observed in UUO mice. On the other hand, significant mitochondrial depolarization, decreased mitochondrial dehydrogenases activity, mitochondrial permeabilization, and decreased adenosine triphosphate and GSH/GSSG levels were discovered in mitochondria isolated from the kidneys of UUO mice. The data obtained from the current study demonstrated a pivotal and interconnected role for oxidative stress and mitochondrial dysfunction in the pathogenesis of renal injury in UUO model. Therefore, these directions could serve as therapeutic targets in animal models or patients of acute renal failure.

Aim of the study:Cholestasis/cirrhosis could induce erythrocyte lysis. The incidence of various types of anemia in cirrhosis is approx. 75%. Several studies have mentioned the pivotal role of oxidative stress in this complication. Taurine (TAU) is the human body's most abundant free amino acid. TAU is known as a robust cell membrane stabilizer. Many studies have mentioned that TAU could counteract oxidative stress in various experimental models. The current study was intended to evaluate the effect of TAU on erythrocytes in cirrhotic rats.Material and methods:Bile duct ligation (BDL) surgery was carried out on rats. Then, complete blood count (CBC), hemoglobin (Hgb), hematocrit (HTC), and erythrocytes' G6PD, catalase (CAT), and superoxide dismutase (SOD) activity were measured. Moreover, biomarkers of oxidative stress were assessed, and the erythrocytes' morphological changes were monitored in the cirrhotic mice exposed to TAU (0.25%, 0.5%, and 1% w : v in drinking water).Results:Significant changes in the assessed erythrocyte parameters (G6PD activity, Hgb, HTC, and erythrocyte count) and red blood cells (RBC) morphological alterations were detected on day 42 after BDL surgery. Biomarkers of oxidative stress also did not change at the time points, except on post-BDL days 28 and 42. A significant decrease in blood parameters was evident at post-BDL day 42. All doses of TAU (0.25%, 0.5%, and 1% w : v in drinking water) significantly improved erythrocyte parameters and encountered oxidative stress in the erythrocytes of cirrhotic animals.Conclusions:These data indicate that TAU could be a safe agent to mitigate cirrhosis-induced erythrocyte damage and anemia. Further investigations are necessary to prove this in clinical settings.

Considering the importance of onions consumption in the household diet, controlling of heavy elements' concentration in foodstuffs is important to ensure the safety of an individual's health. This study aimed to evaluate the risk of heavy metals through onion consumption on human health. In this cross-sectional experimental study, 22 onion samples with varieties red, yellow, and white in the two autumn and winter seasons in 2020 were randomly collected from the different provinces of Kurdistan, Hamedan, and Kermanshah. The concentrations of heavy metals were evaluated with an atomic absorption spectrometer. The risks of human health were evaluated by the hazard quotient (HQ) and the obtained results were analyzed with one-way ANOVA and one sample t-test. The obtained findings demonstrated that all collected samples contained heavy metals. For example, the cadmium (Cd) concentration in onion samples in the province of West Azerbaijan, Kurdistan, Hormozgan, Isfahan, and Zanjan was 526.49, 274.49, 69.77, 67.39, 65.69 mu g kg(-1), respectively. While the standard specified in Iran for the concentration of Cd in onions is 50 mu g kg(-1). However, the rate of lead (Pb) contamination in samples collected from Isfahan, Hormozgan, Zanjan Khuzestan, Tehran (Varamin) was 296.50, 266.71, 261.49, 215.64, 106.19 mu g kg(-1), respectively, which less than maximum allowable limit recommended by WHO-FAO (300 mu g kg(-1)). The HQ for non-cancerous diseases for Cd and Pb were 8.6 x 10(-2) and 1.6 x 10(-1), respectively, and the probability of carcinogenic risk for Pb (8.1 x 10(-4)) was at the level of acceptable. There is no concern about the non-carcinogenic diseases and carcinogenic risk of consuming heavy metals in onion. Therefore, for optimal management and prevention of further pollution, it is recommended to study the origin and determine the amounts of heavy metals for their potential contamination of foodstuffs from the region's soil, water, and dust.

Lead (Pb) is a highly toxic heavy metal widely dispersed in the environment because of human industrial activities. Many studies revealed that Pb could adversely affect several organs, including the male reproductive system. Pb-induced reproductive toxicity could lead to infertility. Thus, finding safe and clinically applicable protective agents against this complication is important. It has been found that oxidative stress plays a fundamental role in the pathogenesis of Pb-induced reprotoxicity. Glycine is the simplest amino acid with a wide range of pharmacological activities. It has been found that glycine could attenuate oxidative stress and mitochondrial impairment in various experimental models. The current study was designed to evaluate the role of glycine in Pb-induced reproductive toxicity in male mice. Male BALB/c mice received Pb (20 mg/kg/day; gavage; 35 consecutive days) and treated with glycine (250 and 500 mg/kg/day; gavage; 35 consecutive days). Then, reproductive system weight indices, biomarkers of oxidative stress in the testis and isolated sperm, sperm kinetic, sperm mitochondrial indices, and testis histopathological alterations were monitored. A significant change in testis, epididymis, and Vas deferens weight was evident in Pb-treated animals. Markers of oxidative stress were also significantly increased in the testis and isolated sperm of the Pb-treated group. A significant disruption in sperm kinetic was also evident when mice received Pb. Moreover, Pb exposure caused significant deterioration in sperm mitochondrial indices. Tubular injury, tubular desquamation, and decreased spermatogenic index were histopathological alterations detected in Pb-treated mice. It was found that glycine significantly blunted oxidative stress markers in testis and sperm, improved sperm mitochondrial parameters, causing considerable higher velocity-related indices (VSL, VCL, and VAP) and percentages of progressively motile sperm, and decreased testis histopathological changes in Pb-exposed animals. These data suggest glycine as a potential protective agent against Pb-induced reproductive toxicity. The effects of glycine on oxidative stress markers and mitochondrial function play a key role in its protective mechanism.

Lead (Pb) is a highly toxic heavy metal. Pb exposure could adversely affect many organs, including the male reproductive system. Oxidative stress and mitochondrial impairment play a fundamental role in the pathogenesis of Pb-induced male reproductive system injury. Taurine (TAU) is abundantly found in mammalian bodies. The positive effects of TAU on oxidative stress biomarkers and mitochondrial function have been reported. The current study evaluated the effects of TAU on Pb-induced reproductive toxicity. Mice received Pb (20 mg/kg/day; gavage, 35 consecutive days). Then, sperm indices (quality and quantity) together with sperm kinetics, sperm mitochondrial parameters, testicular and sperm oxidative stress biomarkers, testis and plasma testosterone levels, and the expression of genes involved in the steroidogenesis process have been evaluated. Pb caused significant histopathological alterations and oxidative stress in male mice’s reproductive system and sperm. Moreover, significant mitochondrial function impairment was evident in sperm isolated from Pb-treated mice. Pb exposure also suppressed the expression of StAR, 17β-HSD, CYP11A, and 3β-HSD genes in the male gonad. It was found that TAU (500 and 1000 mg/kg) significantly improved oxidative stress biomarkers in both male gonads and gametes of Pb-treated mice. TAU also significantly restored sperm mitochondrial function and kinetics. The expression of genes involved in steroidogenesis was also higher in TAU-treated animals. These data suggest TAU as an effective agent against Pb-induced reproductive toxicity. The effects of TAU on oxidative stress markers, mitochondrial function, and the steroidogenesis process seem to play a fundamental role in its protective properties. Further studies are warranted to detect the precise protective effects of this amino acid in the reproductive system. Lead (Pb) is a toxic element that adversely affects the male reproductive system. Mitochondrial impairment and oxidative stress have a crucial role in the Pb-induced reproductive toxicity. Taurine (TAU) could considerably improve the reproductive toxicity induced by Pb via enhancing mitochondrial function and mitigating oxidative stress indices. ΔΨ, mitochondrial membrane potential; ATP, adenosine triphosphate

The excessive presence of nitrate in foodstuff can be potentially toxic and carcinogenic to humans. This is because about 80% of the nitrate that enters the human body comes from vegetables. Therefore, the present study determined the nitrate content in agricultural products commonly consumed by Iranians. A total of 222 samples of 19 different varieties of these products, including vegetables (171 samples), cereals (42 samples), and legumes (9 samples), were randomly collected from major grocery stores in different cities in Iran between September 22 and December 15, 2020. The methods of HPLC-UV were used to evaluate the nitrate content. The detection limits (L.O.D.) and limit of quantification (L.O.Q.) were 0.071 and 0.22 mg kg-1, respectively. As a result, the mean nitrate levels in the different samples varied from 1042.50 mg kg-1 in lettuce to 49.90 mg kg-1 in wheat. Potato also had a higher mean nitrate concentration than the standard level. In addition, products such as tomatoes, eggplant, spinach, herbs, and lettuce had significantly lower average nitrate concentrations than the typical values. Moreover, the average nitrate concentration was highest in the central region (492.7 mg kg-1). In contrast, the lowest average nitrate concentration was in the northern region (121.7 mg kg-1) (P < 0.05). Moreover, the highest average nitrate concentration (468.52 mg kg-1) was found in the vegetable group and the lowest in the cereal group (50.40 mg kg-1) (P < 0.05). Taken together, this information could allow the establishment of a database for the quantification of nitrate exposure and its risk-benefit determination in the Iranian population.

Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28 days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.

Aim of the study Cholestasis is the stoppage of bile flow that primarily affects liver function. On the other hand, kidneys are also severely influenced during cholestasis. Cholestasis-induced kidney injury is known as cholemic nephropathy (CN). There is no precise pharmacological option in CN. Previous studies revealed that oxidative stress plays a crucial role in the pathogenesis of CN. On the other hand, the positive effects of pentoxifylline (PTX) against renal injury with different etiologies have been frequently reported. In the current study, the potential nephroprotective role of PTX in cholestasis-induced renal injury is investigated. Material and methods Bile duct ligated (BDL) rats were treated with PTX (10, 50, and 100 mg/kg), and renal markers of oxidative stress, urine level of inflammatory cytokines, as well as renal histopathological alterations were monitored. Results Significant changes in oxidative stress markers were detected in the BDL group. On the other hand, it was found that PTX (10, 50, and 100 mg/kg) significantly ameliorated cholestasis-induced oxidative stress in renal tissue. Renal histopathological changes, including interstitial inflammation, tubular atrophy, fibrosis, and cast formation, were detected in the BDL rats. Moreover, urine pro-inflammatory cytokines [interleukin (IL)-1, IL-9, IL-18, tumor necrosis factor α (TNF-α), and interferon γ (INF-γ)] were significantly increased in the cholestatic animals. PTX (10, 50, and 100 mg/kg, 14 days) significantly ameliorated renal histopathological alterations and urine levels of inflammatory cytokines. Conclusions These data indicate a potential nephroprotective role for PTX in cholestasis. The effects of PTX on oxidative stress parameters and the inflammatory response could play a primary role in its renoprotective mechanisms.

AIM OF THE STUDY:Cholestasis is a serious complication affecting other organs such as the liver and kidney. Oxidative stress and mitochondrial impairment are proposed as the primary mechanisms for cholestasis-induced organ injury. Taurine (TAU) is the most abundant free amino acid in the human body, which is not incorporated in the structure of proteins. Several pharmacological effects have been attributed to TAU. It has been reported that TAU effectively mitigated oxidative stress and modulated mitochondrial function. The current study aimed to evaluate the impact of TAU on oxidative stress biomarkers and mitochondrial parameters in the kidney of cholestatic animals.MATERIAL AND METHODS:Bile duct ligated (BDL) rats were used as an antioxidant model of cholestasis. Animals were treated with TAU (500 and 1000 mg/kg, oral) for seven consecutive days. Animals were anesthetized (thiopental 80 mg/kg, i.p.), and kidney and blood specimens were collected.RESULTS:Severe elevation in serum and urine biomarkers of renal injury was evident in the BDL group. Significant lipid peroxidation, reactive oxygen species (ROS) formation, and protein carbonylation were detected in the kidney of BDL animals. Furthermore, depleted glutathione reservoirs and a significant decrease in the antioxidant capacity of renal tissue were detected in cholestatic rats. Renal tubular atrophy and interstitial inflammation were evident in BDL animals. Cholestasis also caused significant mitochondrial dysfunction in the kidney. TAU significantly prevented cholestasis-induced renal injury by inhibiting oxidative stress and mitochondrial impairment.CONCLUSIONS:These data indicate TAU as a potential therapeutic agent in the management of cholestasis-induced renal injury.

Cirrhosis-induced renal injury or cholemic nephropathy (CN) is a serious clinical complication with poor prognosis. CN could finally lead to renal failure and the need for organ transplantation. Unfortunately, there is no specific pharmacological intervention against CN to date. On the other hand, various studies mentioned the role of oxidative stress and mitochondrial impairment in the pathogenesis of CN. The current study aimed to evaluate the potential protective effects of NAC as a thiol-reducing agent and antioxidant in CN. Bile duct ligation (BDL) was used as a reliable animal model of cholestasis. BDL animals received NAC (0.25% and 1% w: v) in drinking water for 28 consecutive days. Finally, urine, blood, and kidney samples were collected and analyzed. Significant elevation in serum biomarkers of renal injury, along with urine markers of kidney damage, was evident in the BDL group. Moreover, markers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, protein carbonylation, and increased oxidized glutathione (GSSG) were evident detected in the kidney of cholestatic rats. Renal tissue antioxidant capacity and reduced glutathione (GSH) were also significantly depleted in the BDL group. Significant mitochondrial depolarization, depleted ATP content, and mitochondrial permeabilization was also detected in mitochondria isolated from the kidney of cholestatic animals. Renal histopathological alterations consisted of significant tissue fibrosis, interstitial inflammation, and tubular atrophy. It was found that NAC (0.25 and 1% in drinking water for 28 consecutive days) blunted histopathological changes, decreased markers of oxidative stress, and improved mitochondrial indices in the kidney of cirrhotic rats. Moreover, serum and urine biomarkers of renal injury were also mitigated in upon NAC treatment. These data indicate a potential renoprotective role for NAC in cholestasis. The effects of NAC on cellular redox state and mitochondrial function seem to play a fundamental role in its renoprotective effects during CN.

Objective(s): Manganese (Mn) is an essential trace element physiologically incorporated in the structure of several vital enzymes. Despite its essentiality, excessive Mn exposure is toxic with brain tissue as the primary target organ. There is no specific and clinically available therapeutic/preventive option against Mn neurotoxicity. Carnosine is a neuropeptide with several physiological roles. The neuroprotective properties of this peptide have been evaluated in different experimental models. The current study was designed to investigate the effect of carnosine supplementation and its potential mechanisms of action in an animal model of Mn-induced neurotoxicity.Materials and Methods:Male C57BL/6 mice received Mn (100 mg/kg, s.c) alone and/or in combination with carnosine (10, 50, and 100 mg/kg, i.p). Several locomotor activity indices were monitored. Moreover, biomarkers of oxidative stress and mitochondrial function were assessed in the brain tissue of Mn-exposed animals.Results:Significant locomotor dysfunction was revealed in Mn-exposed animals. Furthermore, brain tissue biomarkers of oxidative stress were significantly increased, and mitochondrial indices of functionality were impaired in Mn-treated animals. It was found that carnosine supplementation (10, 50, and 100 mg/kg, i.p) alleviated the Mn-induced locomotor deficit. Moreover, this peptide mitigated oxidative stress biomarkers and preserved brain tissue mitochondrial functionality in the animal model of manganism.Conclusion:These data indicate that carnosine is a potential neuroprotective agent against Mn neurotoxicity. Antioxidative and mitochondria protecting effects of carnosine might play a fundamental role in its neuroprotective properties against Mn toxicity.

Imatinib is a tyrosine kinase inhibitor widely administered against chronic myeloid leukemia. On the other hand, drug-induced kidney proximal tubular injury, electrolytes disturbances, and renal failure is a clinical complication associated with imatinib therapy. There is no precise cellular mechanism(s) for imatinib-induced renal injury. The current investigation aimed to evaluate the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of imatinib nephrotoxicity. Rats received imatinib (50 and 100 mg/kg, oral, 14 consecutive days). Serum and urine biomarkers of renal injury and markers of oxidative stress in the kidney tissue were assessed. Moreover, kidney mitochondria were isolated, and mitochondrial indices, including mitochondrial depolarization, dehydrogenases activity, mitochondrial permeabilization, lipid peroxidation (LPO), mitochondrial glutathione levels, and ATP content were determined. A significant increase in serum (Creatinine; Cr and blood urea nitrogen; BUN) and urine (Glucose, protein, gamma-glutamyl transferase; γ-GT, and alkaline phosphatase; ALP) biomarkers of renal injury, as well as serum electrolytes disturbances (hypokalemia and hypophosphatemia), were evident in imatinib-treated animals. On the other hand, imatinib (100 mg/kg) caused an increase in kidney ROS and LPO. Renal tubular interstitial nephritis, tissue necrosis, and atrophy were evident as tissue histopathological changes in imatinib-treated rats. Mitochondrial parameters were also adversely affected by imatinib administration. These data represent mitochondrial impairment, renal tissue energy crisis, and oxidative stress as possible mechanisms involved in the pathogenesis of imatinib-induced renal injury and serum electrolytes disturbances.

Manganese (Mn) is a trace element involved in many physiological processes. However, excessive Mn exposure leads to neurological complications. Although no precise mechanism(s) has been found for Mn-induced neurotoxicity, oxidative stress and mitochondrial injury seem to play a relevant role in this complication. On the other hand, there is no protective strategy against Mn neurotoxicity so far. Taurine is an amino acid with significant neuroprotective properties. The current study was designed to evaluate the effect of taurine supplementation and its potential mechanism(s) of action in a mouse model of manganism. Animals were treated with Mn (100 mg/kg, s.c) alone and/or in combination with taurine (50, 100, and 500 mg/kg, i.p, for eight consecutive days). Severe locomotor dysfunction along with a significant elevation in brain tissue biomarkers of oxidative stress was evident in Mn-exposed mice. On the other hand, it was revealed that mitochondrial indices of functionality were hampered in Mn-treated animals. Taurine supplementation (50, 100, and 500 mg/kg, i.p) alleviated Mn-induced locomotor deficit. Moreover, this amino acid mitigated oxidative stress biomarkers and preserved brain tissue mitochondrial indices of functionality. These data introduce taurine as a potential neuroprotective agent against Mn neurotoxicity. Antioxidative and mitochondria protecting effects of taurine might play a fundamental role in its neuroprotective properties against Mn toxicity.