Exposure to two or more compounds in a living system may result in unexpected outcomes. The present study was planned to investigate the effect of two pesticides, Imidacloprid (IMI) and Carbendazim (CBZ), when exposed alone and in combination, on hematological indicators. All mice were equally divided into six different groups consisting of normal control, IMI-L & IMI-H (45.5 & 90.0 mg/kg feed, respectively), CBZ-L & CBZ-H (1.4 and 2.8 g/kg feed, respectively) alone, and in combination (IMI-L+CBZ-L). Blood was collected, and hematology was performed upon completion of the 28-day feeding period. Results revealed that exposure to IMI and CBZ did not show apparent signs and symptoms of toxicity except for the IMI high dose alone. The net average feed and water consumption per mouse were comparatively less in the IMI-H and CBZ-H groups compared to the control group. A dose-dependent significant change (p<0.05) in TLC, TEC, PCV, and Hb values was noticed in treatment groups. Non-significant changes (p>0.05) in the percent lymphocyte, eosinophil, and monocyte were noticed between all the treatment groups. No significant change (p>0.05) in the values of Hb, PCV, MCV, and MCH of the IMI-L+CBZ+L treated group was noticed when compared with the respective IM-L and CBZ-L groups. A non-significant change (p>0.05) in studied parameters was noticed when compared between IMI-L+CBZ-L treated groups with corresponding CBZ-L and IMI-L alone treatment groups. Based on the interactive index, the study concluded that a combination of IMI and CBZ exposure via the dietary medium has no definitive additive or synergistic toxic effect on hematological indicators.

Rhipicephalus microplus (Acari: Ixodidae) is a highly invasive tick responsible for significant economic losses to cattle industry worldwide. The increasing global reports on acaricide resistant tick populations warrant development of alternate eco-friendly approaches for suppressing the tick populations and vectored pathogens. The present study aimed to evaluate the acaricidal activity of essential oils (EOs): Cedar oil (CO), Garlic oil (GO), Peppermint oil (PO) and their combinations against R. microplus by larval packet test. Six concentrations each of individual EOs and their combinations (10, 5, 2.5, 1.25, 0.625 and 0.31

Mancozeb is a commonly used fungicide in agriculture, and its impact on reproductive health remains a subject of concern due to its widespread use. In the pursuit of understanding the potential hazards associated with pesticide exposure, the present study was undertaken to investigate the deleterious effects of subacute oral exposure to Mancozeb on the reproductive system of male Wistar rats. To assess the effects, a comprehensive evaluation was conducted, encompassing various reproductive parameters. A total of 12 healthy Wistar rats were procured and divided into two groups: Group I (Control) and Group II (Treatment), each consisting of six animals. In Group II, Mancozeb was orally administered at a dose of 500 mg.kg-1 body weight for 28 consecutive days, while the control group provided with adlib feed and water without any treatment. Repeated exposure to Mancozeb resulted in alteration in various reproductive health parameters. The exposure produced mild to moderate signs of toxicity and a significant (p

The current investigation aimed to find how exposure to lead and flubendiamide affected the amounts of thyroid hormone levels in buffalo calves’ blood. For ninety days, male buffalo calves were given lead acetate orally at a rate of 9.2 mg/kg bw/day and flubendiamide orally at a rate of 0.024 mg/kg bw/day, either in combination or separately. T3 and T4 levels in blood decreased in response to both flubendiamide and lead exposure alone. When lead and flubendiamide were administered together, the animals’ T3 and T4 levels declined less than when lead and flubendiamide were administered separately. TSH activity increased markedly in rats exposed to both lead and flubendiamide, but not consistently in animals treated with flubendiamide alone. Results of the present study indicated thyrotoxic potential of flubendiamide and lead in buffalo calves. However, further study is required to elucidate the mechanism of thyrotoxic potential of flubendiamide and to understand the interactive effects of these two toxicants on thyroid function in mammals.

Abstract The effect of a combination of two pesticides, carbendazim (CBZ) and imidacloprid (IMI), was investigated on mesenchymal stem cells derived from the bone marrow of buffalo (bMSCs). The bMSCs were exposed to the CBZ (2.25 µM, 4.49 µM, and 8.98 µM) and IMI (0.81 mM, 1.61 mM, and 3.22 mM) alone as well as in combinations. The bMSCs were found to be positive for the stem cell markers, AP, CD73, and OCT4. The bMSCs showed a significant reduction (p ≤ 0.05) in cell viability, and status of anti-oxidants while a significant increase (p ≤ 0.05) in the level of LDH, ALP, and CK-MB in CBZ and IMI-treated groups. A significant increase (p ≤ 0.05) was noticed in LPO, O2─ radical, total ROS, loss of ΔΨm, apoptotic index, and DNA damage in CBZ and IMI-treated groups. A low-dose combination group showed an elevated effect compared to the groups treated with the single pesticide. The interaction index was calculated for CBZ-IMI combined treatment groups on various parameters that showed the majority of antagonist effects. Present findings confirmed that CBZ and IMI-induced cytotoxicity in bMSCs was mediated via ROS production, altered ΔΨm and LPO along with depressed antioxidant status which was responsible for cell apoptosis and cell damage. This study suggested that CBZ and IMI had a dose-dependent toxic effect when the pesticides were used alone, while, co-exposure to both the pesticides simultaneously had an antagonist or non-additive effect on buffalo bMSCs at lower dose combinations and they induced a potentiating effect at high-dose combination.

Cardiovascular disorders are the leading cause of death globally. Rosuvastatin is a member of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase) with many pleiotropic properties. This study investigated cardioprotective effects of rosuvastatin in isoprenaline-induced myocardial injury. Male rats were given rosuvastatin (1, 5, or 10 mg/kg, oral) daily for 1 week and on seventh and eighth day isoprenaline (150 mg/kg, subcutaneous) was given to induce cardiac injury. On ninth day, rats were euthanized and different samples were harvested for analysis. Isoprenaline administration resulted in increased cardiac mass, increased cardiac injury marker levels (cTnI, CK-MB, ALT, and AST), increased lipid/protein oxidation, and increased cardiac nitrite levels. It also decreased superoxide dismutase, CAT, GST, and glutathione reductase activities, and total antioxidant activity. Isoprenaline also increased TNF-α and IL-6 levels. Decreased mRNA expression of Nrf2 and Bcl-2 along with increased mRNA expression of Bax, eNOS and iNOS genes was observed in isoprenaline treated animals. Histopathological evaluations of rosuvastatin pre-treated groups showed reduction of myocardial necrosis. Pretreatment with rosuvastatin (5 and 10 mg/kg) reduced many of these pathological changes. The current study showed that rosuvastatin significantly reduces myocardial injury induced by isoprenaline.

Estrogen and progesterone congeners as found in various oral contraceptive formulations have been implicated as the cause of cancer in sex and tissue-specific targets. The mechanism of carcinogenesis by sex steroids is still debatable. In this study, we evaluated the genotoxicity induced by two components of one of the commonly used oral contraceptive formulation; drospirenone and ethinylestradiol in human breast cells (MCF-7) in vitro and in bone marrow cells of female mice in vivo. DNA damage was assessed by alkaline comet assay. Both of the drugs produced DNA damage in human breast cells at exposure concentrations which are about 100-fold and above than normally found in human blood after their lowest recommended doses. The DNA damage was produced only after metabolic activation by mice liver S-9 fraction in both cases. The co-exposure with both the compounds at median exposure levels resulted in potentiation of DNA damage. In bone marrow cells of adult female mice, both the compounds produced DNA damage at human equivalent doses after exposure was carried out repeatedly for approximately one estrus cycle (5 days). The co-administration with the compounds resulted in potentiation of DNA damage as indicated by percent tail DNA in comet assay. Thus it is concluded that drospirenone and ethinylestradiol cause DNA damage in certain target specific tissue (mammary epithelial cells) and in female bone marrow cells. The co-exposure with drospirenone and ethinylestradiol results in potentiation of genotoxicity which may pose a threat of cancer development in women taking these drugs for long periods.

The presence of one or more pesticides in a variety of mediums is responsible for their indirect toxicological events leading to cell senescence. In the present investigation, the endeavor was made to see the effect of pesticides Car- Benda-Zim (CBZ) and IMIdacloprid (IMI) alone and in combination with bone marrow-derived Mesenchymal Stem Cells (bMSCs) of buffalo origin. Isolated and cultured bMSCs were exposed to CBZ and IMI alone and in combinations at lower doses. Cells were observed for alterations in cell morphology, oxidative stress, mitochondrial damage and cellular senescence. bMSCs characterized for stem cell surface markers and found to be positive for AP, CD73 and OCT4. bMSCs exposed to IC25, IC12.5 and IC6.25 CBZ and IMI alone and combinations of IC12.5 and IC6.25 of CBZ and IMI. Results revealed significant reduction (p?0.05) in cell viability noticed on microscopic examination along with loss of normal cell morphology and increased in Reactive Oxygen Species (ROS) positive cells, cells with loss of ??m and number of senescent cells in CBZ and IMI treated groups. Lower dose combination groups showed elevated effects when compared with higher dose alone treated groups and control groups. Present findings suggest that CBZ and IMI induced cytotoxicity in bMSCs mediated via ROS production, altered ??m leading to the cell damage and predisposing senescence process. Moreover, the co-existence of CBZ and IMI in a medium has a considerably more toxic effect than their individual effect.

The present study involved the investigation of various leaf extracts of Citrullus colocynthis (bitter apple) viz. alcoholic, acetone and chloroform for their in vivo anti-inflammatory and in vitro antibacterial and acaricidal activities. For in vivo evaluation, doses of the extracts were taken as 50 mg/kg and 100mg/kg and for in vitro experiments, concentrations @5% and 10 % were used in the study. The antibacterial activity was studied against gram +ve (Staphylococcus aureus) and gram –ve (Escherichia coli) bacteria and was compared with standard drug (ampicillin). For anti-inflammatory activity; fifty rats were divided into 10 groups of five animals each. Initially the normal paw volumes of all the animals were noted down. All animals were injected in the sub-planter region of the right hind paw with 1% carrageenan (in normal saline) @ 0.1 ml to induce inflammation. The acaricidal activity of the alcoholic leaf extract was investigated by Adult immersion test against engorged adult females of Rhipicephalus microplus (Canestrini, 1888) (Acari: Ixodidae). No dose-dependent acaricidal activity of the extracts was demonstrated as there was no mortality of the ticks and absence of significant inhibition of oviposition by any of the concentrations of the extracts. Also the results revealed no significant antibacterial activity but all the extracts demonstated significant anti-inflammatory activity with maximum activity in alcoholic extract at higher concentration.

Background: The antipyretic, analgesic and anti-inflammatory activities of two concentrations (100 and 200 mg/kg) of ethanolic extract of leaf, bark, flower and fruit pulp of C. fistula were determined in male wistar albino rats. Methods: Antipyretic activity was assessed by E. coli endotoxin induced pyrexia. Analgesic activity was assessed by hot plate, tail immersion and acetic acid induced writhing test. Anti-inflammatory activity was evaluated by carrageenan-induced rat paw edema assay. Result: Significant (p less than 0.05) antipyretic activity was exhibited from 2h onwards by bark extract @ 200 mg/kg and from 3h onwards by bark extract @100 mg/kg and leaves extract @ 200mg/kg as compared to control group. Significant (p less than 0.05) analgesic activity was shown by extract of bark @ 200 mg/kg as it is evident by increase in reflex time in hot plate (90,120,180 min), tail immersion test (120,180 min) and inhibition of writhing (32.12%). Significant (p less than 0.05) anti-inflammatory activity was exhibited from 3h post administration by bark @ 200 and leaves @ 100 and 200 mg/kg.

Pharmacokinetics of cefquinome was studied in febrile female goats following its intravenous (IV) administration at the dose rate of 2 mg/kg body weight. The fever was induced by administration of Escherichia coli lipopolysaccharide (lμg/kg body weight). Cefquinome concentration in plasma of goats was estimated using HPLC. The drug was detected upto 24 h in febrile goats. The disposition kinetics of the drug was described by twocompartment open model. PK-PD indices; AUC24h/MIC, Cmax/MIC, T>MIC were calculated by integrating in-vivo PK data with earlier generated MIC data against Pasteurella (P.) multocida. A favourable PK and PK-PD indices suggested that the dose of 2 mg/kg/24 h of cefquinome would be effective clinically to treat goats affected with P. multocida infections.

The present study investigated the potential of different leaf extracts of Bitter Apple (Citrullus colocynthis) as an analgesic agent and In-vitro cytoprotective ameliorative effects of the various extracts in thiomethoxam-induced toxicity in MDBK cell lines. Different leaf extracts of Citrullus colocynthis i.e. alcoholic, acetone and chloroform were investigated for analgesic activity at the dose rate of 50 mg/kg and 100 mg/kg in Wistar rats. For the assessment of analgesic activity, tail flick method was used. In-vitro cytoprotective activity of various leaf extracts (at concentrations of 5% and 10%) was evaluated in ATCC acquired MDBK cell lines and for this study, cytotoxicity was induced by thiomethoxam. For cytoprotective study, oxidative stress parameters- catalase, LPO, SOD and GPx were determined. Study on analgesic activity revealed the presence of dose dependent effect in all extracts with highest effect in alcoholic extract of Bitter Apple. It is believe that triterpene alkaloids and steroidal principles present in the plant products might be responsible for the analgesic effect.

Different leaf extracts of Citrullus colocynthis Schrad., i.e., alcoholic, acetone and chloroform were investigated for antipyretic activity, muscle relaxant activity and neurobehavioural activity at the dose rate of 50 mg/kg and 100 mg/kg in wistar rats. Antipyretic activity was evaluated using E. coli lipopolysacharide (2 mu g/kg). For muscle relaxant activity, rota-rod apparatus was used and fall-off time was noted. For the assessment of neurobehavioural profile, elevated plus maze was used and anxiolytic responses produced by the extracts were noted. Rodents (rats and mice) have an aversion for open spaces and prefer enclosed ones, therefore spend more time in enclosed spaces (thigmotaxis). Time spent in open and closed arms was automatically recorded by the camera attached to the computer through software. In evaluation of antipyretic activity, alcoholic extract @ 100 mg/kg showed maximum response when compared to control as temperature started to decrease after 2 h of drug administration and came to normal after 5 h. However, present study revealed no muscle relaxant and neurobehavioural activity of different leaf extracts of C. colocynthis as none of the extracts showed any significant change in the evaluation parameteres when compared to the control group.

The objective of this study was to investigate the pharmacokinetics of cefquinome in 5 healthy male dromedary camels following a single intramuscular (IM) administration at the dose rate of 1 mg/kg body weight in the caudal cervical epiaxial muscles. Blood samples were collected prior to drug administration and up to 48 h after drug administration. No clinical symptoms or signs suggestive of adverse drug reaction could be recorded in any animal. Plasma cefquinome concentration was estimated by high-performance liquid chromatography. The disposition kinetics of cefquinome best fitted to a 2 compartment open model. The peak plasma cefquinome concentration (C-max cal) of 1.013 +/- 0.038 mu g/ml(-1) was achieved at 5.257 +/- 0.067 h (t(max cal)). The absorption half-life (t(ka)(1/2)), elimination half-life (t(beta)(1/2)), area under plasma drug concentration-time curve (AUC) and apparent volume of distribution (Vd(area)) of cefquinome were 3.401 +/- 0.042 h, 3.754 +/- 0.072 h, 14.417 +/- 0.621 mu g/ml(-1) h and 0.379 +/- 0.016 l/kg(-1), respectively. The results of the present study suggested that an intramuscular dosage regimen of 1 mg/kg body weight at 24 h interval would maintain the plasma drug levels required to be effective against the common bacterial pathogens in dromedary camel.

Hypothyroidism is a common disorder of small ruminants and is expected to alter the pharmacokinetics of drugs. Hypothyroidism was induced by feeding thiourea at the dose rate 50 mg.kg-1 daily for 28 days to goats. Disposition of lincomycin, after intravenous administration at dose rate 10 mg/kg, was investigated in hypothyroid goats to determine the potential dosage regimen against susceptible microorganisms. Blood samples were collected from 1 min to 24 h of drug administration. The drug was detected in plasma up to 8 h and lincomycin was rapidly distributed from blood to the tissue, as evidenced by the high value of the distribution coefficient (mean ± SEM) 12.3±1.09 h-1. The large Vd (1.78±0.18 L/kg) indicated vast tissue distribution of lincomycin in goats. The elimination half life, AUC and total body clearance were 3.99± 0.25 h, 33.2±1.71 ìg.h/mL and 0.31±0.02 L/h/kg, respectively. Based on results, lincomycin in hypothyroid goats is suggested to be repeated at 12 h interval for organisms sensitive to lincomycin having MIC up to 0.1 µg.ml-1.

Present review article reveals the importance of Bitter Apple belonging to the species Citrullus colocynthis, distributed in India and other parts of the world; this extensive research information on this species is highly significant for future researchers worldwide.As per Ayurveda and Siddha system of medicine it is Tikta-rasam, ushna-veeryam and katuvipakam and used as purgative, diuretic, lagu, kapharam and abortifacient.Fruit is bitter, pungent and used as purgative, anthelmintic, antipyretic, carminative, cures tumors, leucoderma, ulcers, asthma, etc. Root is useful in jaundice, ascites, urinary disease, rheumatism.In this article pharmacological and biological activity, inputs have been extensively recorded and discussed. K e y w o r d sBitter apple, Citrullus colocynthis (L.) Schrad.(Cucurbitaceae)

The single dose pharmacokinetics (PK) of marbofloxacin was compared with repeated intravenous (IV) administrations in six healthy goats at the dose rate of 2 mg/kg body weight at 24 h interval for 5 days. Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t(1/2elm) = 4.37 +/- 0.18 h and Cl-B = 0.29 +/- 0.01 following single administration were not significantly different from t(1/2elm) = 5.11 +/- 0.22 h and Cl-B = 0.26 +/- 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 mu g/mL and 0.4 mu g/mL. The AUC(0-24h)/MIC ratios were 226.64 +/- 7.21 h for E. coli and 16.99 +/- 0.541 h for P. multocida. PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC <= 0.03 mu g/mL) infections. However, a higher dose of 6 mg/kg/day is suggested to obtain clinical cure against diseases caused by P. multocida having MIC90 = 0.12 mu g/mL in goat species.

Flubendiamide is a recently introduced, fast-acting insecticide with an excellent residual effect. In an unpublished study, it was reported not to cause any genotoxic, carcinogenic and neurotoxic effects in mammals. However, recent studies suggest that it is toxic for fish and Chinese tiger frog. Alterations in leukogram, erythrocytic indices and aspartic acid concentration in cerebrospinal fluid in water buffalo following its chronic exposure to flubendiamide have also been recorded in our laboratory.

Different leaf extracts of Pongamia pinnata L., i.e., aqueous, alcoholic, acetone and chloroform were investigated for antipyretic activity, muscle relaxant activity and neurobehavioural activity at the dose rate of 50 mg/kg and 100 mg/kg in wistar rats. Antipyretic activity was evaluated using E. coli LPS (2 mu g/kg). For muscle relaxant activity, rota-rod apparatus was used and fall-off time was noted. For the assessment of neurobehavioural profile, elevated plus-maze was used and anxiolytic responses produced by the extracts were noted. Rodents (rats and mice) have an aversion for open spaces and prefer enclosed ones, therefore, spend more time in enclosed spaces (thigmotaxis). Time spent in open and closed arms was automatically recorded by the camera attached to the computer through software. In evaluation of antipyretic activity, aqueous extract @ 100 mg/kg showed maximum response when compared to control. However, present study revealed no muscle relaxant and neurobehavioural activity of different leaf extracts of P. pinnata.

The aim of the present study was to develop and characterize ceftriaxone loaded BSA nanoparticles. The nanoparticles were prepared by desolvation method. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and fourier transform infrared (FT-IR) characterization of the synthesized nanoparticles was done. SEM and TEM revealed that the nanoparticles had a smooth and spherical surface and FT-IR revealed that there was no interaction between the drug and the polymer. Encapsulation efficacy of nanoparticles was 44.8%. The mean particle size of BSA obtained was 149.46 ± 1.05 nm, PDI was 0.09 and the zeta potential was -28 mV. In vitro drug release at pH 7.4 was found to be 85.8% at 12 h time period. Various mathematical models were used and the values nearest to R2 were evaluated. Model fitting revealed that it followed the Higuchi and Korsmeyer Peppas Model. The values of R were higher for Higuchi and Korsmeyers peppas model. Pharmacodynamic studies were done, for S. aureus the results of MIC and MBC of Drug were 2.51 μg and 3 μg. The results of MIC and MBC of sample were 1.51 μg and 2.1 μg and for E. coli the results of MIC and MBC of Drug were 0.05 μg and 0.08 μg. The results of MIC and MBC of sample were 0.05 μg and 0.05 μg.