Ferulic acid exerts a protective effect against cyclosporine-induced liver injury in rats via activation of the Nrf2/HO-1 signaling, suppression of oxidative stress, inflammatory response, and halting the apoptotic cell death.

Drug-induced liver injury is one of the main challenges that leads to the withdrawal of several drugs in the clinical setting. Cyclosporine is one of the drugs that its long-term administration exerts devastating effects on the hepatocytes. In the present study, we aimed to evaluate the effect of ferulic acid, a natural compound found in plants, on cyclosporine-mediated hepatotoxicity. Forty-eight male Wistar rats were treated with cyclosporine and/or ferulic acid to evaluate the function as well as the morphology of liver cells. We found that ferulic acid dose-dependently recovered the functional as well as histopathological parameters of liver cells, as revealed by the improvement of hepatocellular vacuolation, portal fibroplasia, and necrosis. Moreover, this phenolic compound was able to restore the balance of the redox system in cyclosporine-treated rats by activating the nuclear factor (NF) erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling axis. Of note, the protective effects of ferulic acid against cyclosporine-mediated liver toxicity were not restricted only to induction of the potential antioxidant property, as in the presence of this agent, the expression of pro-inflammatory cytokines such as NF-κB, tumor necrosis factor (TNF)-α, and interleukin-1ß was also diminished. Ferulic acid also shifted the equilibrium between the expression levels of proapoptotic to antiapoptotic proteins and thereby prevented the development of cyclosporine-induced liver injury. Overall, these findings highlighted that ferulic acid can reduce cyclosporine-induced liver injury due to its antioxidant properties.

Designing a novel multi­epitope vaccine against Ebola virus using reverse vaccinology approach.

Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings.

Ferulic acid prevents cyclosporine-induced nephrotoxicity in rats through exerting anti-oxidant and anti-inflammatory effects via activation of Nrf2/HO-1 signaling and suppression of NF-κB/TNF-α axis.

Cyclosporine is one of the main immunosuppressive agents used in the treatment of autoimmune diseases or transplantation. Despite the favorable effects, cyclosporine-mediated nephrotoxicity critically restricts the clinical use of the agent. Given this, herein, we aimed to evaluate whether ferulic acid could prevent cyclosporine-mediated nephrotoxicity in rats. A total of 32 Wistar rats were chosen to be treated with cyclosporine, ferulic acid, and the combination of both agents for 21 days. To evaluate the nephron-protective mechanism of ferulic acid, the serum levels of biochemical parameters, as well as the tissue levels of several oxidative and anti-oxidative mediators, were examined. The expression and the tissue levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, heme oxygenase (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2) were evaluated using the qRT-PCR and ELISA, respectively. Our results showed while cyclosporine elevated the serum levels of renal-related markers in the rats, in the presence of ferulic acid, there was a significant reduction in the levels of urea, uric acid, creatinine, and sGOT. Moreover, we found that ferulic acid remarkably prevented cyclosporine-mediated nephrotoxicity by restoring the anti-oxidant system through activating the Nrf2/HO-1 axis. By halting the NF-κB-mediated upregulation of TNF-α, it also seems that ferulic acid prevented lymphocytes infiltration into kidney tissue and consequently suppressed inflammatory responses. Overall, the results of the present study suggest that due to the anti-oxidant and anti-inflammatory properties of ferulic acid, this agent could be used alongside cyclosporine to reduce its adverse effects on kidney tissue.

Synergistic Effects of Lauryl Gallate and Tamoxifen on Human Breast Cancer Cell.

BACKGROUND: Tamoxifen (TAM) is widely used for adjuvant therapy in breast cancer patients. Tamoxifen therapy may lead to serious side effects. Anti-apoptotic substances in combination with chemotherapy drugs can result in additive or synergistic effects. Lauryl gallate (LG), a Gallic acid derivative, has been proven to inhibit tumor growth, without affecting normal cells. This study aimed to investigate the synergistic effect of TAM and LG in breast cancer cell line (MCF-7). METHODS: In this experimental study, performed in ShahreKord University of Medical Science, Iran in 2017, the MCF-7 cells were treated by final concentrations of 10 µM TAM alone, and in combination with 200 µM of LG. We also used EX-527, as SIRT-1 inhibitor to examine the role of SIRT1 in cell apoptosis. BCL-2 and SIRT1 gene expression were measured by real-time PCR method, and cell apoptosis was investigated by flow cytometry. RESULTS: Tamoxifen alone and in combination with LG decreased BCL-2 expression 2.64±0.75 and 6.38±1.9 fold, respectively, after 48 h (P<0.05). SIRT1 expression was increased 1.67±0.22 and 2.47±0.34 - fold by TAM alone and in combination with LG, respectively (P<0.05). TAM alone and in combination with LG increased the percentage of apoptotic cells 15.79±2.81 and 60.67±6.23 percent, respectively after 48 h (P<0.001). CONCLUSION: The combination of LG and TAM is more effective for induction of apoptosis of breast cancer cells, compared to individual use of each. Thus, our data pave the way for new therapeutic options for suppressing breast cancer growth.

Modulatory effects of artichoke (Cynara scolymus L.) leaf extract against oxidative stress and hepatic TNF-α gene expression in acute diazinon-induced liver injury in rats.

Background Diazinon (DZN) causes serious liver damage in both humans and animals. In the present study, the hepatoprotective effects of Cynara scolymus L. leaf extract against DZN-induced liver injury were examined. Methods Forty male rats were divided into five groups. The control group received a normal diet. The DZN group received DZN only (25 mg/kg, po). The DZN + Syl group received DZN (25 mg/kg, po) and silymarin (Syl) (50 mg/kg, po). The DZN + Art group received DZN (25 mg/kg, po) and artichoke (Art) leaf extract (1500 mg/kg, po). The Art group received Art leaf extract only (1500 mg/kg, po). After 15 days, serum tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lipid profile, protein carbonyl content, serum and hepatic malondialdehyde (MDA), hepatic TNF-α gene expression, hepatic catalase (CAT), superoxide dismutase (SOD), and vitamin C (Vit C) were measured and histopathological examination was performed. Results DZN caused a significant elevation in serum ALP, AST, ALT, MDA, TNF-α, protein carbonyl, hepatic MDA, and TNF-α gene expression in the DZN group as opposed to the control group. Also, DZN led to the reduction of hepatic CAT, SOD, and Vit C in the DZN group relative to the control group. The administration of Art extract resulted in not only a significant reduction in serum ALP, AST, ALT, MDA, TNF-α, and protein carbonyl but also an improvement of liver histopathological changes and hepatic CAT and SOD activities as opposed to the DZN group. Conclusions This study confirmed that Art leaf extract has liver protective effects and causes downregulation of oxidative stress in acute DZN-induced liver injury in rats.

Effects of Pioglitazone On the Lipid Profile, Serum Antioxidant Capacity, and UCP1 Gene Expression in Mouse Brown Adipose Tissue.

BACKGROUND: Pioglitazone increases insulin sensitivity and improves glycemic control in type 2 diabetics. In this study, we evaluated the effects of pioglitazone on the uncoupling protein 1 (UCP1) expression in mouse brown adipose tissue (BAT), and on recovery from oxidative stress due to a high-fat diet. METHODS: 30 mice were divided into three groups: group 1 received a normal diet, group 2 received a high-fat diet, and group 3 received a high-fat diet plus 30 mg/kg pioglitazone. After treatment, the cholesterol, triglyceride, paraoxonase 1 (PON1), total serum antioxidant capacity (TAC), malondialdehyde (MDA), and specific activity of hepatic catalase were measured. BAT UCP1 expression was evaluated at both the mRNA and protein levels. RESULTS: The weights differed between the groups (p<0.05). Serum MDA was greater and TAC, liver catalase, and PON1 were less than in group 2 than in group 1 (p<0.05). In Serum MDA was less and catalase activity was greater in group 3 than in group 2 (p<0.05). UCP1 gene expression was less in group 2 than in group 1 (p<0.05) but greater than in group 3 (p<0.05). CONCLUSION: Pioglitazone may have a protective role in high-fat-diet-induced oxidative stress by increasing the antioxidant capacity. Moreover, it can induce weight loss by increasing UCP1 mRNA and protein expression.

Effects of Nigella sativa Extracts on the Lipid Profile and Uncoupling Protein-1 Gene Expression in Brown Adipose Tissue of Mice.

BACKGROUND: Uncoupling protein-1 (UCP-1) is the index protein of the brown adipose tissue (BAT), used in the obesity studies. We evaluated the effects of thymoquinone (TQ), hydroalcoholic, and hexane extracts of Nigella sativa, on the UCP-1 gene expression in BAT, and also on the recovery from oxidative stress, due to a high-fat diet. MATERIALS AND METHODS: Fifty mice were divided into five groups: the first group was fed with a usual diet and the second, third, fourth, and fifth groups with a high-fat diet, hydroalcoholic extract, hexane extract, and TQ, respectively. After completing the course, the lipid profile, paraoxonase 1 (PON1), serum total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. UCP-1 expression in BAT was evaluated at the gene and protein level. RESULTS: The weight of mice, receiving TQ, hydroalcoholic, and hexane extracts, was decreased (P < 0.05), compared to the second group (P < 0.05). MDA was increased in the second group, compared to the first group (P < 0.05); however, TAC, liver catalase enzyme, and PON1 were decreased (P < 0.05). Furthermore, MDA of the third, fourth, and fifth groups had decreased, and the activity of PON1, liver catalase enzyme, and the amount of TAC was increased (P < 0.05). UCP-1 expression of the third and fourth groups was increased, compared to the second group (P < 0.05). CONCLUSION: The results suggest that TQ, hydroalcoholic, and hexane extracts of N. sativa have a protective and therapeutic role in the oxidative stress, caused by high-fat diets. The hydroalcoholic and hexane extracts can induce weight loss, by positively affecting UCP-1, at the gene and protein level.

The effect of resveratrol on expression of matrix metalloproteinase 9 and its tissue inhibitors in vascular smooth muscle cells.

BACKGROUND: Matrix metalloproteinase 9 (MMP-9) is involved in extracellular matrix degradation and remodeling. An increase in MMP-9 expression by vascular component cells plays an important role in atherosclerotic plaque formation and rupture. Resveratrol, a polyphenolic substance, was suggested to play a role in preventing the progress of atherosclerotic disease. The aim of this study was to investigate the effect of resveratrol on MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) in vascular smooth muscle cells (VSMCs) after treatment with H2O2. METHODS: Cultured VSMCs were pre-treated with 0.2 mM of H2O2 before stimulation with different concentration of resveratrol. Expression of MMP-9, TIMP-1, and TIMP-3 genes were measured using real-time polymerase chain reaction (PCR) method, and MMP-9 protein level was detected using western blot analysis. RESULTS: Resveratrol at 120 µmol/l concentration reduced the elevated level of MMP-9 induced by H2O2 in VSMCs as 1.85 ± 0.35 folds (P < 0.050) and 8.70 ± 1.20 folds (P < 0.050) after 24 and 48 hours, respectively. Resveratrol increased the diminished level of TIMP-1 induced by H2O2 as 2.5 ± 0.48 folds following the treatment with 120 µmol/l after 48 hours (P < 0.050). CONCLUSION: Resveratrol as an antioxidant can decrease MMP-9 production, not only by suppressing MMP-9 expression, but also by augmenting TIMP-1 production. Altogether, resveratrol as an antioxidant can regulate the MMP-9/TIMP-1 balance, and may be considered as a preservative agent in the treatment and prevention of atherosclerosis.

Evaluation of the effects of the hydroalcoholic extract of Terminalia chebula fruits on diazinon-induced liver toxicity and oxidative stress in rats.

OBJECTIVE: Diazinon causes oxidative stress and dysfunction of the liver. This study was undertaken to evaluate the effects of the hydroalcoholic extract of Terminalia chebula, on some biochemical and histopathological parameters of liver tissue in diazinon-administered rats. MATERIALS AND METHODS: Wistar rats were orally administered with 25 mg/kg body weight diazinon. Vehicle (distilled water) and silymarin (50 mg/kg body weight) were used as the negative and positive control groups, respectively. Diazinon-administered groups were treated with T.chebula (Terminalia chebula) fruit extract (200, 400, and 800 mg/kg). After 15 days of treatment, the blood specimens and liver samples were examined. RESULTS: In diazinon-treated group, the levels of serum urea, high density lipoprotein (HDL), and liver superoxide dismutase (SOD), catalase (CAT), and vitamin C significantly decreased (p<0.05) compared to control. Also, in this group, serum triglyceride (TG), total cholesterol (TC), very low density lipoprotein cholesterol (VLDL), protein carbonyl (PC), malondialdehyde, tumor necrosis factor-α (TNF-α), and TNF-α gene expression significantly increased (p<0.05) as compared to the control (vehicle-treated rats). Treatment with T. chebula resulted in a significant increase (p<0.05) in CAT, SOD, vitamin C, HDL and a significant decrease (p<0.05) in the level of urea, MDA, PC, TG, TC, VLDL, TNF-α protein, and the gene expression of TNF-α compared with test without treatment group. Histopathological evidence demonstrated that treatment with T. chebula extract could decrease liver lymphocyte infiltration. CONCLUSION: The present study suggests that T. chebula fruit extract has protective effects against diazinon-induced oxidative stress.

Comparison of Pure Palm Olein Oil, Hydrogenated Oil-Containing Palm, and Canola on Serum Lipids and Lipid Oxidation Rate in Rats Fed with these Oils.

BACKGROUND: Due to increased consumption of canola oil and hydrogenated oil containing palm and palm olein, and their possible effects on serum lipoproteins, the present study was conducted to determine the effects of these oils on lipids and lipid oxidation level. METHODS: In this experimental study, 88 Wistar rats were randomly assigned to four groups. Control group (A) was on a normal diet. Groups B, C, and D, in addition to normal diet, were fed with hydrogenated oil-contained palm oil, pure palm olein oil, and canola oil, respectively for 4 weeks. Serum Biochemical factors [total cholesterol (TC), triglyceride (TG), LDL, HDL, LDL/HDL ratio, oxLDL, paraoxanase-1 (PON1), and malondialdehyde (MDA)] were measured. RESULTS: The lowest mean serum TC was seen in the control group and the highest in the group B. There were differences in TC, TG, HDL, MDA, and PON1 between the control group and other groups (P<0.001). The lowest and highest LDL/HDL ratios were observed in the group C and the control group, respectively. Significant differences were seen in OxLDL and PON1 between the control group and other three groups (P<0.05), while there were no significant differences in oxLDL and PON1 among the other three groups (P>0.05). MDA was higher in groups C and D. CONCLUSION: Canola oil, hydrogenated oil-containing palm and palm olein may increase atherosclerosis risk through decreasing PON1 activity and elevating oxLDL. Palm olein oils in rats' diets cause a considerable decrease in LDL and help to increase HDL.

Nephroprotective and Anti-Inflammatory Effects of Pistacia atlantica Leaf Hydroethanolic Extract Against Gentamicin-Induced Nephrotoxicity in Rats.

Gentamicin in overdose can lead to tubular injury and kidney dysfunction. Some antioxidants can protect kidneys against nephrotoxicity. This study was undertaken to evaluate the protective effects of Pistacia atlantica (P. atlantica) leaf hydroethanolic extract against gentamicin-induced nephrotoxicity in rats. Forty rats were divided into five groups: the first group received a daily intraperitoneal (i.p.) injection of normal saline. The second group received gentamicin (120 mg/kg, i.p.). The third, fourth, and fifth groups were orally treated with 200, 400, and 800 mg/kg of P. atlantica leaf hydroethanolic extract, respectively, and they also received gentamicin (120 mg/kg, i.p.). After seven days, serum malondialdehyde (MDA), creatinine (Cr), urea, uric acid, lipids profile, protein carbonyl (PC), and tumor necrosis factor-α (TNF-α) were determined. Also, a piece of kidney was used to determine catalase (CAT) and superoxide dismutase (SOD) activities, vitamin C, the gene expression of TNF-α, and for subsequent histopathological studies. Treatment with P. atlantica leaf hydroethanolic extract resulted in a significant increase (p < 0.05) in CAT, SOD, vitamin C, and high-density lipoprotein cholesterol, and significantly decreased (p < 0.05) the levels of Cr, urea, uric acid, MDA, PC, triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, TNF-α protein, and the gene expression of TNF-α compared with the untreated group. Histopathological studies show that in lymphocyte infiltration, remarkable reduction was observed in P. atlantica leaf hydroethanolic extract-treated groups, compared with the untreated group. The present study suggests that P. atlantica leaf hydroethanolic extract has protective effects against gentamicin-induced nephrotoxicity.

The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells.

Prostate cancer (PC) is one of the most common cancers among men. Progression of prostate cancer is associated with an increase in cellular level of interleukin-6 (IL-6). Gallic acid (GA) is a polyhydroxy phenolic compound which can inhibit the growth of cancer cells. The aim of this study was to evaluate the effects of GA treatment on cell viability, proliferation, invasion, IL-6 gene expression, IL-6 secretion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins in human prostate cancer PC3 cells. PC3 cells viability after treatment with GA (0-120µM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of IL-6 was investigated using real-time polymerase chain reaction. Cellular concentration of pSTAT3, pERK1/2, and pAKT signaling proteins were determined by Western blotting technic. PC3 cells invasion was assessed by invasion assay test. Treatment with GA caused a significant decrease in cell viability, proliferation, invasion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins after 48h in a dose-dependent manner. The level of IL-6 and its gene expression decreased significantly in PC3 cells treated with GA. Our results show that IL-6 down-regulation and decreased IL-6 protein level in PC3 cells by GA resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins which lead to the reduction of the cell survival, proliferation, and invasion in PC3 cells. Therefore, it seems that GA can be considered an anticancer agent in the treatment of prostate cancer.

Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

Iron overload in ß-thalassemia major occurs mainly due to blood transfusion, an essential treatment for ß-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in ß-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to ß-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for ß-thalassemia major patients.

Adiponectin inhibits oxidized low density lipoprotein-induced increase in matrix metalloproteinase 9 expression in vascular smooth muscle cells.

BACKGROUND: High expression of matrix metalloproteinase 9 (MMP9) during vascular injury and inflammation plays an important role in atherosclerotic plaque formation and rupture. In the process of atherosclerosis, oxidized low-density lipoprotein (oxLDL) upregulates MMP9 in human aortic vascular smooth muscle cells (HA/VSMCs). Adiponectin is an adipose tissue-derived hormone that has been shown to exert anti-atherogenic and anti-inflammatory effects. The aim of this study was to investigate the effect of adiponectin on MMP9 expression under pathogenic condition created by oxLDL in HA/VSMCs. METHODS: In this experimental study, HA/VSMC were stimulated with oxLDL alone and in the presence of adiponectin for 24 and 48 h. The expression of MMP9 gene was determined by real-time polymerase chain reaction method. The protein level of this gene was investigated by western blotting technique. RESULTS: An oxLDL increased MMP9 expression 2.16 ± 0.24- and 3.32 ± 0.25-fold after 24 and 48 h, respectively and adiponectin decreased oxLDL-induced MMP9 expression in a time-dependent manner. CONCLUSION: These results show that adiponectin changes extracellular matrix by reducing MMP9 mRNA and protein, therefore, may stabilize lesions and reduce atheroma rupture.

The effect of adiponectin on osteonectin gene expression by oxidized low density lipoprotein-treated vascular smooth muscle cells.

Osteonectin is a bone- associated protein involved in vascular calcification. Adiponectin may protect against cardiovascular disease but possible effects on vascular calcification have been poorly studied. The aim of this study was to investigate the modulatory effect of adiponectin on oxidized low density lipoprotein (oxLDL)- induced expression of osteonectin in human aorta vascular smooth muscle cells (HA/VSMCs). HA/VSMCs were cultured in F12K media and then treated with oxLDL (100 µg/mL) in the presence or absence of adoponectin (5 µg/mL) for 24 and 48 hours. mRNA expression and protein level of osteonectin were determined by quantitative real-time PCR and western blot analysis, respectively. After exposure to oxLDL, osteonectin expression increased 1.62 ± 0.23- and 6.62 ± 0.48-fold after 24 and 48 hours respectively compared to the control. Adiponectin increased oxLDL- induced osteonectin expression in a time-dependent manner after 24 and 48 hours (3.24 ± 0.39- and 24.93 ± 2.15-fold, respectively). Western blotting confirmed that osteonectin protein was upregulated by adiponectin.Our data suggest that OxLDL might cause the increase of osteonectin expression both at mRNA and protein level. This upregulation is intensified by adiponectin.

I405V and -629C/A polymorphisms of the cholesteryl ester transfer protein gene in patients with coronary artery disease.

BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a main role in high-density lipoprotein metabolism. CETP gene possesses several single nucleotide polymorphisms which have been associated with plasma high-density lipoprotein cholesterol (HDL-C) concentrations. The aim of this study was to determine the association of CETP -629C/A and I405V polymorphisms with coronary artery disease (CAD) in Iranian population. METHODS: The presence of two CETP gene polymorphisms -629C/A and I405V were studied in 187 unrelated CAD cases and 136 controls. All the samples were clinically examined and lipid profile was estimated. Genotyping was performed using polymerase chain reaction/restriction fragment length polymorphism method. RESULTS: The frequency of -629C/A and I405V allelic variants were found to be 0.732 and 0.366 in cases and 0.658 and 0.348 in controls, respectively. The frequency of A allele of -629C/A polymorphism in cases was significantly higher than that of controls. HDL-C in AA genotype was higher than CA and CC genotypes in controls. No significant effect of II, IV and VV genotypes was found in lipid profiles. CONCLUSION: No significant association was found between CETP I405V polymorphism and increased risk of CAD in Azeri population studied. AA genotype of -629C/A increased HDL but the risk of CAD in this genotype might be higher than CC genotype.