OBJECTIVES:There has been a sharp increase in the use of e-cigarettes and heated tobacco products (HTPs) in the last decade. Related to the increase in the use, serious public health debates have been caused by the safety and risks of these products. Particularly due to the exposure to a lot of toxic substances, including heavy metals, there has been an increasing concern over their health effects. Heavy metals such as lead, arsenic, mercury, and cadmium are environmental pollutants poising significant health risks. These metals have a disposition to accumulate in the human body over time. Even at lower levels of exposure, they might lead to multiple organ damage and adverse health effects, including neurotoxicity, nephrotoxicity, and being carcinogenicity. This study tests the idea that using electronic cigarettes (e-cigarettes) and IQOS devices raises the levels of metals in urine and that the amount of increase depends on which product is used. The study aims to look at the levels of lead, cadmium, nickel, zinc, and selenium in the urine of cigarette smokers, e-cigarette users, IQOS users, and nonsmokers; to check for significant differences in metal levels between these groups (with a significance level set at p < 0.05); to compare the metal levels found with safety limits; and to explore if there's a link between the metal levels in urine and the type of product used (cigarettes, IQOS, or e-cigarettes). METHOD:This study aimed to compare the trace element, heavy element, and nicotine exposures of individuals who smoke (n = 39), use e-cigarettes (n = 28), use IQOS (n = 20), and do not use tobacco or tobacco products (n = 30) while living in Ankara, Türkiye. In order to evaluate the element levels of the participants, the levels of lead, cadmium, nickel, zinc, and selenium metals in their urine were determined using inductively coupled plasma mass spectrometry (ICP-MS), and nicotine exposures were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS:The measurement showed that lead levels were higher in IQOS users (8.51 ng/g creatinine) and smokers (3.67 ng/g creatinine) compared to e-cigarette users (1.38 ng/g creatinine), and this difference was statistically significant (p < 0.05). In addition, a statistically significant difference was found between the cotinine level and lead level of the smoking and IQOS groups (p ˂ 0.05). No statistically significant difference was found between the groups in terms of cadmium level (p > 0.008). Nickel level was found to be higher in e-cigarette (3.43 ng/g creatinine) and IQOS (3.84 ng/g creatinine) users than in the smoking group (0.99 ng/g creatinine). In terms of nickel, a statistically significant difference was found between the e-cigarette and IQOS groups and both the smoking and control groups (p ˂ 0.05). No statistically significant difference was found between the selenium level and both the groups and the cotinine level (p > 0.008). Zinc levels were higher in IQOS users (596.13 ng/g creatinine) than in e-cigarette users (298.40 ng/g creatinine) and cigarette users (217.59 ng/g creatinine). No statistically significant difference was found between the cotinine levels of e-cigarette, IQOS, and cigarette users (p > 0.05). CONCLUSION:This study investigated metal exposure profiles by comparing urinary metal concentrations across different groups of tobacco product users (cigarette smokers, IQOS users, and e-cigarette users). The findings revealed that lead and cadmium levels were significantly higher in cigarette smokers compared to nonsmokers. In contrast, elevated nickel concentrations were notably observed among IQOS and e-cigarette users. Variations in zinc and selenium levels appeared to be more attributable to physiological or external factors rather than product use. Overall, the results suggest that both conventional and novel tobacco products may pose potential toxicological risks related to metal exposure among users. However, the observed metal concentrations generally fell below established regulatory thresholds.

Objectives:This study investigated the impact of a high-fat diet streptozotocin (STZ)-induced diabetes and dapagliflozin treatment on hepatic protein expression of CYP3A4.Materials and Methods:In our study, 34 male Sprague-Dawley rats were randomly divided into four groups: Control, high-fat diet and STZ-induced diabetes, dapagliflozin-treated control, and dapagliflozin-treated diabetes. In the microsomes obtained from the livers of these rats, the protein expression levels of CYP3A4 were determined by Western blotting.Results:Hepatic CYP3A4 protein expression levels in the control group treated with dapagliflozin were significantly decreased compared with those in the control group. In addition, hepatic CYP3A4 protein expression levels were decreased in dapagliflozin-treated diabetic Sprague-Dawley rats compared with those in both control and diabetic group rats, but the difference between the groups was not statistically significant.Conclusion:According to these two results, the use of dapagliflozin inhibited hepatic CYP3A4 protein expression.

The goal of this study is to synthesize and test a series of novel benzimidazole derivatives (3 a-3 q, 4 a, 4 b) for antimicrobial and antioxidant activity. The compounds were tested for antimicrobial activity in vitro using the macro dilution broth method. The antioxidant activity of the synthesized compounds was evaluated using assay of Lipid peroxidation (LP) level by measuring the formation of 2-thiobarbituric acid reactive substances (TBARS) and 7-Ethoxyresorufin O-deethylase (EROD) activity. Only the compound 3 m demonstrated significant antimicrobial activity against all of the microorganisms tested. The LP level of compound 3 m (5.20 +/- 0.28, 68 %) was comparable to that of standard BHT (5.68 +/- 0.22, 65 %). Compounds 3 i (11 %, 28 %) and 3 m (13 %, 32 %) are the most active compounds on microsomal EROD activity and LP levels which are better than standard caffeine (15 %) and BHT (35 %), respectively. Also compounds 3 g (20 %), and 4 b (28 %) have much better LP levels than BHT (35 %). Compound 3 m exhibited high docking energies scores comparing with reference drugs when docked with bacterial Penicillin-Binding Protein 3 and 4, sterol 14 alpha-demethylase of C. albicans and urate oxidase enzyme.

Traditional two-dimensional (2D) cell culture employed for centuries is extensively used in toxicological studies. There is no doubt that 2D cell culture has made significant contributions to toxicology. However, in today's world, it is necessary to develop more physiologically relevant models. Three-dimensional (3D) cell culture, which can recapitulate the cell's microenvironment, is, therefore, a more realistic model compared to traditional cell culture. In toxicology, 3D cell culture models are a powerful tool for studying different tissues and organs in similar environments and behave as if they are in in vivo conditions. In this review, we aimed to present 3D cell culture models that have been used in different organ toxicity studies. We reported the results and interpretations obtained from these studies. We aimed to highlight 3D models as the future of cell culture by reviewing 3D models used in different organ toxicity studies.

Objectives: The in vitro antioxidant properties of some 2-(2-phenyl)-1H-benzo(d)imidazol-1-yl)-N'-(arylmethylene) acetohydrazide derivatives (1-12) were investigated in this study. Materials and Methods: The in vitro antioxidant activity of compounds 1-12 was explored by determination of rat liver microsomal nicotinamideadenine dinucleotide phosphate dependent inhibition on lipid peroxidation (LPO) levels and microsomal ethoxyresorufin O-deethylase (EROD) activity. Results: All synthesised compounds had LPO inhibitory activity (15-57%) except compound 6, which contains a thiophene ring. Almost all the compounds displayed slightly inhibitory activity (2-20%) on EROD. Conclusion: The most active compound, 3 bearing a p-bromophenyl substituent at the second position of the benzimidazole ring, caused 57% inhibition of LPO level, while butylated hydroxytoluene showed 65% inhibition. None of the synthesised compounds had a marked inhibitory effect on EROD activity.

Reactive oxygen species (ROS) and lipid peroxidation (LPO) levels may increase in diabetic state and lead to oxidative stress, which plays a critical role in the progression of diabetes. There are various sources of ROS, including cytochrome P450 monooxygenases (CYP450s), which may be modulated in terms of their activities and expressions under diabetic conditions. This study is aimed to investigate the effects of streptozotocin-induced diabetes and insulin treatment on hepatic cytochrome P450 1A1 (CYP1A1) and cytochrome P450 2E1 (CYP2E1) activities and LPO levels. Methods: CYP1A1 and CYP2E1 activities were measured with ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, respectively. LPO levels were then corroborated via thiobarbituric acid reactive substances. Results: In diabetic rats, a marked 2.1- and 2.4-fold increase in hepatic CYP1A1 activity and 1.8- and 1.6-fold increase in hepatic CYP2E1 activity were observed compared to controls and insulin-treated diabetic rats, respectively. Hepatic LPO levels in diabetic rats did not significantly change compared to controls. However, in insulin-treated diabetic rats, LPO levels are 0.92- and 0.89-fold remarkably decrease compared to controls and diabetics, respectively. Conclusion: The present study suggests that insulin might have a useful role in the modulation of CYP1A1 and CYP2E1 activities as well as LPO levels in the liver of diabetic rats.

Tobacco smoke from regular cigarettes contains a number of harmful chemicals such as nicotine, arsenic, benzene, carbon monoxide, heavy metals, and tobacco-derived nitrosamines. About 1% of over 7000 chemical substances formed by burning tobacco are identified as the leading causes or possible risk factors of smoking-related diseases such as lung cancer, cardiovascular diseases, and emphysema. The concept of heating tobacco without combustion and smoke has been designed for more than two decades. The products developed with this idea, known as "Heat-Not-Burn" tobacco cigarettes, were first introduced in the late 1980s but did not achieve commercial success. However, the tobacco giants have been trying to remarket tobacco heating systems with new technological and modified features for over 10 years. I-Quit-Ordinary-Smoking (iQOS®) is one of the latest heat-not-burn tobacco products, first launched in Japan and Italy. The company then made a submission to the Food and Drug Administration as a modified-risk tobacco product application to sell its own tobacco-heating device iQOS® under its Marlboro® brand in the USA with reduced-risk claims in 2016, but it was rejected. This device is, however, now sold in more than four dozen countries. There are some striking claims that iQOS®, which is described as a novel hybrid product between traditional cigarettes and electronic cigarettes, offers an alternative way to substantially reduce the amount of harmful components compared with traditional cigarettes by its new technology in which tobacco is heated up to 350°C instead of being burnt. It is claimed to produce vapour containing nearly 90% less toxic substances than cigarette smoke and not be a source of second-hand smoking negatively affecting indoor air quality. The purpose of this article is to objectively review the potential effects of iQOS® on human health and the environment by searching and integrating the published research findings.

This review summarizes recent information concerning the pharmacological and toxicological significance of the flavin-containing monooxygenases (FMOs). FMOs are a family of microsomal enzymes involving in the oxygenation of certain xenobiotics and drugs containing nucleophilic heteroatoms. The activities of FMOs in drug metabolism and their relationships with diseases are the areas of research requiring further exploration. Future studies on FMOs may provide considerable information about the pathophysiology of diseases and the information related to this enzyme family may be important for drug designs in future.

OBJECTIVES:To synthesize and characterize 4-(substituted benzylidene)-2-(substituted phenyl)oxazol-5(4H)-one derivatives (E1-E10), and evaluate them for antioxidant activity.MATERIALS AND METHODS:Required oxazole-5(4H)-one derivatives were synthesized in two steps to obtain novel hippuric acid derivatives (7-13); glycine and acylated appropriate benzoic acid derivatives were used and then, final compounds were obtained with condensation of 7-13 with appropriate benzaldehydes (E1-E10). These products were purified by column chromatography using ethyl acetate/n-hexane as eluent. All the compounds were unequivocally characterized using the combination of 1H and 13C-nuclear magnetic resonance, mass spectrometry (ESI-MS), and elemental analysis. The inhibition of lipid peroxidation and its effects on hepatic cytochrome P450-dependent ethoxyresorufin-O-deethylase (EROD) enzyme were determined in rats in vitro.RESULTS:The most active analogue on the microsomal EROD activity was E3 which inhibited the microsomal EROD activity (89%) and was similarly better than that of the specific inhibitor caffeine (85%) at 10-3 M concentration.CONCLUSION:The findings of this study indicate that the synthesized compounds, such as E3, display significant antioxidant activity.

The most important enzyme system of phase I metabolism is cytochrome P450, a superfamily of hemecontaining mono-oxygenases and responsible for the metabolism of drugs, xenobiotics, environmental compounds, carcinogens and several endogenic compounds (1,2). These enzymes are abundant in the liver, it also exists in some extrahepatic tissues such as kidney, lung, intestine and brain (4). Total CYP levels in the brain are low and approximately 0,5-2% of those in the liver (2). CYPs are distributed homogeneously in the liver whereas each of CYP450 isoenzymes is located according to their specific localization in the brain (3). Therefore, it is difficult to determine the enzymatic activity of CYPs in the brain.

In this study, some novel 5-[[2-(phenyl/p-chlorophenyl)-benzimidazol-1-yl]-methyl]-N-substituted phenyl-1,3,4-oxadiazol-2-amine derivatives (28-45) with an oxadiazole ring were synthesized. The antioxidant properties and radical scavenging activities of the compounds were investigated employing various in vitro systems: hepatic microsomal NADPH-dependent inhibition of lipid peroxidation levels, scavenging of DPPH free radicals, and inhibition of microsomal ethoxyresorufin O-deethylase activity (EROD). Compounds 34 and 41 were found to be good scavengers of DPPH radicals (76% and 84%) when compared to BHT (90%). Almost all of the compounds examined were found to possess a good inhibitor effect on the microsomal EROD activity. Moreover, 32 and 41 were more active analogs (97% and 98%) on the microsomal EROD activity than caffeine (85%).

In this study, the optimum conditions (pH, amount of protein, substrate concentration, incubation time) of a cytochrome P450 dependent enzyme, coumarin 7-hydroxylase (COH), activity were determined in microsomal fractions of mouse liver and brain. It’s indicated that different reaction conditions are required for this enzyme activity in mouse liver and brain microsomes. The results obtained, reveal the requirement of optimization studies on COH activity for different tissues of mouse.

In recent years, extensive investigations on neurodegenerative disorders has been providing considerable information about the relationship between environmetal toxins and CYP450 enzymes. A chemical neurotoxin, MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), can lead to Parkinson’s disease in C57BI/6 mouse model. CYP2E1 is a substantial enzyme involved in the metabolism of xenobiotics in brain and liver. It’s also known to generate reactive oxygen species and promote oxidative stress causing many diseases such as Parkinson’s Disease, Alzheimer Disease, atherosclerosis. CYP2E1 is expressed in brain less than liver however brain CYP2E1 contributes to progression of diseases. Evidence for involvement of CYP2E1 in the MPTP induced mouse model of Parkinson’s Disease has been reported. In the present study, brain and liver CYP2E1 activities are compared between control and parkinsonism groups of C57BI/6 and Swiss albino mice. CYP2E1 protein expressions are evaluated by the method of Western blotting in these goups. Also brain and liver CYP2E1 activities and protein expressions are compared between Swiss albino and C57BI/6 mice. In this study, we monitored various profiles for different mouse species in the context of CYP2E1 activities and expressions.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and affects up to 2% of individuals after the age 65. It is characterized by progressive motor decline and loss of dopaminergic neurons from the substantia nigra (SN) leading resting tremor, rigidity, bradykinesia and postural instability. Differential characteristics of PD pathology is the loss of dopaminergic neurons and the presence of intracellular protein aggregates. The etiology of the disease is still unknown and it is likely due to a multifactorial interaction of genes and the environmental factors on the background of ageing. The impact of enzyme activities, gene expressions and genetic polymorphisms in GSTs on PD has received particular interest since these enzymes play an important role in the detoxification and metabolism of several environmental chemicals and xenobiotics which may be associated to PD. Patients with idiopathic PD appear to have reduced capacity for detoxification and/or metabolism of certain environmental compounds such as cigarette smoke and pesticides. Therefore we aimed to examine GST theta, mu, pi and total GST activities by the use of ENPP, EAA, DCNB and CDNB as substrates, respectively in a MPTP induced animal (mouse) model of Parkinson’s disease. In the same animal model we also investigated the gene expression levels of GSTM1 and GSTP1 using the method of qPCR. As a result, we observed an increase in cytosolic GST teta (GSTT) and cytosolic total GST activity which are statistically significant. qPCR results indicated an significant increase for GSTP1 mRNA expression level.

Parkinson Hastaligi (PH) 65 yas ustu populasyonun % 2'den fazlasini etkileyen, Alzheimer'dan sonra gorulen ikinci en yaygin norodejeneratif hastaliktir. Substantia Nigradaki (SN) noron kaybiyla karakterize olup beraberinde dinlenme halinde tremor, rijidite, bradikinezi ve postural bozukluk gibi belirtiler gozlenmektedir. Hastaligin patalojisinin ayirdedici ozelligi dopaminerjik noron kaybi ve Lewy cisimcigi olarak bilinen hucre ici protein agregatlarinin varligi olmakla birlikte etiyolojisi henuz tam olarak aydinlatilabilmis degildir. PH'nin patogenezinde arkaplanda yaslanmayla birlikte genetik ve cevresel bircok faktorun rol oynadigi dusunulmektedir. Bugune kadar hayvan ve insanda yapilmis cok sayida calisma vardir. Ancak Parkinson Hastaligina (PH) neden olan birincil sebepler hala bilinememektedir. Bircok gen mutasyonunun ve delesyonunun PH'nin patogenezinde rol oynadigi dusunulmektedir. GST'ler ve CYP450'ler PH ile iliskisi olabilecegi dusunulen cevresel kimyasalllarin ve ksenobiyotiklerin detoksifikasyonunda ve metabolizmasinda rol oynadigindan gerek genetik polimorfizmleri gerek enzim aktiviteleri ve gen ekspresyonulariyla ilgili calismalar ilgi cekmektedir. Idiyopatik PH tanisi konmus kisilerde, sigara dumani ve pestisitler gibi bazi cevresel bilesikleri metabolize ve/veya detoksifiye etme kapasitelerinin dusuk oldugu gorulmustur. Vaka-kontrol calismasi olarak tasarlanan arastirmada, GST ailesine ait, mu (GSTM1) omega (GSTO1), pi (GSTP1), ve teta (GSTT1) ve CYP450 ailesinden CYP2E1 gen polimorfizmlerine bakilmis, bu genlerin sigara kullanimi ve PH ile iliskileri degerlendirilmistir. Tez kapsaminda, Ankara Egitim ve Arastirma Hastanesi Noroloji Kliniginden saglanan; yas, cinsiyet ve etnik koken olarak uyumlu 68 idiyopatik Parkinson hastasi ve 105 kontrolle calisilmistir. Uygulanan genetik yaklasimlar Multipleks PZR, PZR ve RFLP analiz yontemleridir. Tum bu genetik analizler sonucunda, genotip frekanslari kontrol ve PH gruplari icin sirasiyla, GSTP1 ekzon 6 polimorfizm frekanslari, Ala/Ala (wt) %81,9, %58,8; Ala/Val (h) %18,1, %38,2 ve Val/Val (m) %2,9'dur. Kontrol grubunda Val/Val mutant genotipine rastlanmamistir. GSTP1 ekzon 5 polimorfizm frekanslari Ile/Ile (wt) %42,9, %41,2, Ile/Val (h) %47,6, 47,1% ve Val/Val (m) %9,5, %11,8 bulunmustur. GSTO1 A140D polimorfizm frekanslari A/A (wt), %39, %39,7; A/D (h) %46,7, %45,6 ve D140D (m) % 14,3 ve %14,7 olarak hesaplanmistir. CYP2E1 *5b polimorfizm sonuclari, c1/c1 (wt) %89,5, %94,1; c1/c2 (h) %9,5, %5,9 ve c2/c2 (m) %1'dir. PH grubunda c2/c2 (m) genotipine rastlanmamistir. Son olarak, CYP2E1*6 polimorfizmine ait genotip freakanslari D/D (wt) %81, %86,8, D/C (h) %19, %13,2 bulunmustur. C/C mutant genotipine her iki grupta da rastlanmamistir. GSTP1 ekzon6 Val alleline (OO=2,85, %95 GA: 1,53–5,3) ve GSTT1(+) (OO= 4,04, %95 GA: 1,91–8,57) genine sahip bireylerin PH'ya yakalanma risklerinin kontrole gore anlamli olarak daha fazla oldugu gozlenmistir. Diger polimorfizmler icin herhangi bir anlamlilik gorulmemistir. PH icin, calisilan GST'lerle, CYP2E1*5B, CYP2E1*6 genleri ve sigara arasinda anlamli bir iliskiye rastlanmamistir. Gen-gen etkilesimlerine bakildiginda ise, GSTM1(+) ve GSTT1(+) (OO=2,85, %95 GA: 1,53–5,3) genlerine; GSTP1ek5 (h) veya GSTP1ek6 (h), (OO=2.4, %95 GA: 1,14–5,32); GSTT1(+) and GSTP1ek5 (h/m), (OO=2,5, %95 GA: 1,3–4,7); GSTP1ek6 (h/m) ve GSTO1 (h/m) (OO=5,82, %95 GA: 2,5–13,5); GSTM1 (+) ve GSTT1(+)/GSTP1ek6 (h/m), (OO=9,0 %95 GA: 1,8–44,6); GSTM1 (+) veya GSTT1(+)/GSTP1ek6 (h/m), (OO=9,0 %95 GA: 2,1–38,8); GSTM1(-) ve GSTT1(-)/GSTP1ek6 (h/m), (OO=%8,95 GA: 1,16–55,3) genotiplerine sahip bireylerde PH'ya yakalanma riskinin daha fazla oldugu gozlenmistir. C57BL/6 cinsi Kontrol ve MPTP grubundaki farelerde spesifik aktivitelerin ortanca degerlerine bakildiginda, MPTP uygulanan farelerde CDNB ve ENPP'nin spesifik aktivitelerinin, kontrole gore istatiksel olarak anlamli bir sekilde artis gosterdigi tespit edilmistir. Benzer anlamlilik EAA ve DCNB icin gorulmemistir. Buna gore, ENPP'nin substrat olarak kullanildigi GSTT aktivitesinde kontrole gore 1,13 katlik anlamli bir artis gozlenmistir. CDNB'nin substrat olarak kullanildigi total GST aktivitesinde ise 1,6 katlik anlamli bir artis bulunmaktadir. DCNB'nin substrat olarak kullanildigi GSTM aktivitesindeki 1,13 katlik azalma ve EAA'nin substrat olarak kullanildigi GSTP aktivitesindeki 1,22 katlik artis ise istatiksel olarak anlamli bulunmamistir. MPTP uygulanan farelerde ayni zamanda qPCR yontemi kullanilarak GSTM1 ve GSTP1 genlerinin ekspresyon duzeylerine bakilmistir. GSTP1 mRNA ekspresyon duzeyinin referans gen olarak kullanilan 18S'e gore 1,55 katlik anlamli bir artis gosterdigi gozlenmistir. GSTM1 mRNA ekspresyon duzeyi icin anlamli bir artis gozlenmemistir.AbstractParkinson disease, the second most common neurodegenerative disorder after Alzheimer disease, affecting up to 2% of individuals after the age 65, is characterized by progressive motor decline and loss of dopaminergic neurons from the substantia nigra (SN) leading resting tremor, rigidity, bradykinesia and postural instability. Differential characteristics of PD pathology is the loss of dopaminergic neurons and the presence of intracellular protein aggregates (Lewy bodies). The etiology of the disease is still unknown and it is likely due to a multifactorial interaction of genes and the environmental factors on the background of ageing. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of PD. The impact of genetic polymorphisms, enzyme activities and gene expressions in GSTs and CYP450s on PD has recieved particular interest since these enzymes play an important role in the detoxification and metabolism of several environmental chemicals and xenobiotics which may be associated to PD. Patients with idiopathic PD appear to have reduced capacity for detoxification and/or metabolism of certain environmental compounds such as cigarette smoke and pesticides. Using a case-control study design, we examined polymorphisms of the mu (GSTM1) omega (GSTO1), pi (GSTP1), and theta (GSTT1) classes of GST and CYP2E1 of CYP450 family to elucidate the effects and smoking-GST interactions on PD risk. From Ankara Egitim ve Arastirma Hastanesi Noroloji Klinigi, we recruited 68 idiopathic PD cases, clinically confirmed by our study neurologist and 105 healthy controls, matched by age, gender, and race. PCR/RFLP techniques are applied during the analysis. Results of frequencies for GSTP1 exon 6 polymorphism are, Ala/Ala (wt) 81.9%, 58.8%; Ala/Val (h) 18.1%, 38.2% and Val/Val (m) 2.9% for control and PD groups, respectively. Val/Val mutant genotype is not found for control group. GSTP1 exon 5 polymorphism frequencies are Ile/Ile (wt) 42.9%, 41.2%. Ile/Val (h) 47.6%, 47.1% and Val/Val (m) 9.5%, 11.8%. GSTO1 A140D polymorphism frequencies are calculated as A/A (wt), 39%, 39.7%; A/D (h) 46.7%, 45.6% and D140D (m) 14.3% and 14.7%. CYP2E1 *5b polymorhism results, c1/c1 (wt) 89.5%, 94.1%; c1/c2 (h) 9.5%, 5.9% and c2/c2 (m) 1%. No result for. c2/c2 (m) PD group. Finally results for CYP2E1*6 polymorphism are calculated as D/D (wt) 81% 86.8%, D/C (h) 19%, 13.2%. C/C mutant genotype is not found. We observed an increased risk in subjects carrying Val allele for GSTP1 exon6 (OR=2.85, 95% CI: 1.53–5.3) and GSTT1(+) (OR= 4.04, 95% CI: 1.91–8.57). No significant effects were observed for the rest of polymorphisms. We didn't determined any significant association between cigarette smoking and GSTs studied, CYP2E1*5B, CYP2E1*6. According to the combined gene effects, we observed increased risk for subjects having GSTM1(+) and GSTT1(+) (OR=2.85, 95% CI: 1.53–5.3); GSTP1ex5 (h) or GSTP1ex6 (h), (OR=2.4, 95% CI: 1.14–5.32); GSTT1(+) and GSTP1ex5 (h/m), (OR=2.5, 95% CI: 1.3–4.7); GSTP1ex6 (h/m) and GSTO1 (h/m) (OR=5.82, 95% CI: 2.5–13.5); GSTM1 (+) and GSTT1(+) with GSTP1ex6 (h/m), (OR=9.0 95% CI: 1.8–44.6); GSTM1 (+) or GSTT1(+) with GSTP1ex6 (h/m), (OR=9.0 95% CI: 2.1–38.8); GSTM1(-) and GSTT1(-) with GSTP1ex6 (h/m), (OR=8,95% CI: 1.16–55.3). In addition to the polymorhism studies, GST teta, mu, pi and total GST activities are studied in a MPTP exposed animal model of Parkinsonism. We observed 1.13 fold increase in cytosolic GST teta (GSTT) activity (used ENPP as a substrate) and 1.66 fold increase in cytosolic total GST (GST) activity (used CDNB as a substrate) which are statistically significant. However, 1.22 fold increase in cytosolic GST mu (GSTM) activity (used EAA as a substrate) and 1.13 fold decrease in cytosolic total GST pi (GSTP) activity (used DCNB as a substrate) were not statistically significant. In the same animal model we also investigated the gene expression levels of GSTM1 and GSTP1 using the method qPCR. Our results indicated an significant 1.55 fold relative increase for GSTP1 mRNA expression level according to the reference gene 18S mRNA expression level which was taken as 1. We did't observed any significant increase for GSTM1 mRNA expression level.

Our approach was to synthesize and examine the antioxidant properties of some new 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(2-arylmethyleneamino) acetamide (118) and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl)acetamide (1t18t) derivatives. Their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation levels (LP assay) and microsomal ethoxyresorufin O-deethylase activities (EROD assay) were determined. The free radical scavenging properties of the compounds were also examined in vitro determining the interaction of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The compounds showed significant effects in the above tests.

In this study, two new series of 2-amino-1,3,4-oxadiazoles and 5-aryl-1,3,4-oxadiazoles carrying a benzimidazole moiety were synthesized. The antioxidant properties of these compounds were investigated in vitro by the determination of the microsomal NADPH-dependent inhibition of lipid peroxidation levels (LP), the microsomal ethoxyresorufin O-deethylase activity (EROD), and DPPH radical scavenger effects. Among the tested compounds, 2-[(2-(4-chlorophenyl)-1H-benzo[d]imidazole-1-yl)methyl]-5-(4-fluorophenyl)-1,3,4-oxadiazole (9) was found to be the most active compound in all three in vitro systems.