Association of Nicotine Use Disorder with Neurexin 3 Gene Polymorphisms. / Nikotin Kullanim Bozuklugunun Neurexin 3 Gen Polimorfizmi ile Iliskisi.

OBJECTIVE: In this study, we aimed to investigate the Neurexin 3 gene (NRXN3) polymorphisms in the rs 221473, rs 221497, rs1004212 and rs11624704 regions in relation to nicotine use disorder (NUD) in the Turkish population. METHOD: Power analysis indicated that the NUD group and the control group of this study should each comprise 200 participants in the 18-65 year age range. The NUD group consisted of individuals without a psychiatric first axis disorder except for NUD, mental retardation, past head trauma or a neurological disorder, who had smoked minimally10 cigarettes per day for at least 1 year. The control group included individuals without a serious chronic physical illness, a previous psychiatric disorder or mental retardation and who responded "no" to the question "have you ever smoked?" A sociodemographic questionnaire and the Fageström nicotine dependence scale (FNDS) for the NUD group were utilized. Venous blood samples of all participants were taken into tubes containing EDTA (ethylene daimine tetra acetic acid) for DNA extraction. Duplex fluorescence melting curve analysis was used for genotype detection and differentiation. RESULTS: The individuals carrying the AC allele and the AG allele at the rs11624704 and the rs1004212 regions respectively had a high risk of being addicted to cigarettes. CONCLUSION: This is first study investigating the relationship of the NRXN3 gene and nicotine addiction in the Turkish population. It was observed that the risk of NUD in the Turkish population may be related to the Neurexin gene.

Association of Nicotine Use Disorder with Neurexin 3 Gene Polymorphisms. / Nikotin Kullanim Bozuklugunun Neurexin 3 Gen Polimorfizmi ile Iliskisi.

OBJECTIVE: In this study, we aimed to investigate the Neurexin 3 gene (NRXN3) polymorphisms in the rs 221473, rs 221497, rs1004212 and rs11624704 regions in relation to nicotine use disorder (NUD) in the Turkish population. METHOD: Power analysis indicated that the NUD group and the control group of this study should each comprise 200 participants in the 18-65 year age range. The NUD group consisted of individuals without a psychiatric first axis disorder except for NUD, mental retardation, past head trauma or a neurological disorder, who had smoked minimally10 cigarettes per day for at least 1 year. The control group included individuals without a serious chronic physical illness, a previous psychiatric disorder or mental retardation and who responded "no" to the question "have you ever smoked?" A sociodemographic questionnaire and the Fageström nicotine dependence scale (FNDS) for the NUD group were utilized. Venous blood samples of all participants were taken into tubes containing EDTA (ethylene daimine tetra acetic acid) for DNA extraction. Duplex fluorescence melting curve analysis was used for genotype detection and differentiation. RESULTS: The individuals carrying the AC allele and the AG allele at the rs11624704 and the rs1004212 regions respectively had a high risk of being addicted to cigarettes. CONCLUSION: This is first study investigating the relationship of the NRXN3 gene and nicotine addiction in the Turkish population. It was observed that the risk of NUD in the Turkish population may be related to the Neurexin gene.

In vitro study on immune response modifiers as novel medical treatment options for cholesteatoma.

OBJECTIVES: To investigate cytokine profile of cholesteatoma and to collect information about important intercellular signaling pathways by establishing two different cell culture models, to block important intercellular signaling pathways in cholesteatoma by applying immune system modifier drugs to develop alternative medical therapy options for cholesteatoma. METHODS: To observe the pathogenesis of cholesteatoma and to apply the immunomodulatory drugs, cholesteatoma tissue culture models were constituted with HEKa cells and cholesteatoma keratinocytes, which were obtained from 3 patients who underwent operations for cholesteatoma. Medicines including 5-fluorourasil, imiquimod, cyclosporine, and tacrolimus were applied on both cholesteatoma keratinocytes and HEKa cells. After 48 h of incubation, IL-1, IL-6, IL-8, IL-10, TNF-α, and Ki67 levels were measured to determine cell viability rates. RESULTS: In the cholesteatoma control group, IL-6 and TNF-α levels were found higher than in the HEKa control group. All repurposed drugs in the study demonstrated anti-inflammatory, anti-proliferative, and cytotoxic effects on cholesteatoma. Imiquimod and tacrolimus in particular are potential treatment prospects for cholesteatoma due to their strong anti-inflammatory and cytotoxic effects. CONCLUSION: Medical therapy options for cholesteatoma are still missing and surgery is not the ultimate solution. We have focused on intercellular inflammatory processes, which play significant roles in the pathogenesis of cholesteatoma in our paper. Inflammation and proliferation of cholesteatoma decreased after all repurposed drug applications in our study. Anti-inflammatory and anti-proliferative effects of tacrolimus and imiquimod was more significant than other drugs in the study. For this reason, tacrolimus and imiquimod should be examined in depth with in vivo studies in terms of efficacy and safety for medical treatment of cholesteatoma.

The Effect of Androgens on Proinflammatory Cytokine Secretion from Human Ocular Surface Epithelial Cells.

Purpose: The purpose of this study is to explore the effects of dihydrotestosterone (DHT) on lipopolysaccharide (LPS)-induced proinflammatory cytokine release in human ocular surface epithelial cells exposed to LPS and LPS-binding protein (LBP).Methods: Immortalized human corneal, conjunctival, and meibomian gland epithelial cells were cultured in keratinocyte-free medium. After confluency, they were exposed to a stratification medium Dulbecco's modified Eagle medium (DMEM)/F12 in the presence of fetal bovine serum and were exposed to vehicle, LPS + LBP, or DHT. Culture media were processed for multiplex-bead analysis of specific proinflammatory cytokines including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-8, IL-6, IL-10, IL-1ß, vascular endothelial growth factor (VEGF)-A. Cytokine concentrations were compared by analysis of variance with Tukey post hoc testing. p < 0.05 was considered statistically significant.Results: The results are LPS + LBP-induced the secretion of IFN-γ, IL-6, IL-10, IL-1ß, VEGF-A cytokines in corneal epithelial cells; TNF-α, IL-2, IL-8, IL-6, IL-1ß, VEGF-A cytokines in conjunctival epithelial cells; and IL-8, IL-6, IL-1ß, VEGF-A cytokines in meibomian gland epithelial cells. When these LPS + LBP-stimulated cells were exposed to DHT for 2 days, it was found that DHT suppressed the secretion of IL-6, IL-10, IL-1ß, VEGF-A cytokines in corneal epithelial cells; TNF-α, IL-6, IL-1ß, VEGF-A cytokines in conjunctival epithelial cells; and IL-6, IL-1ß, VEGF-A cytokines in meibomian gland epithelial cells.Conclusion: LPS + LBP is shown to induce the secretion of certain proinflammatory cytokines from ocular surface and adnexal epithelial cells. DHT showed anti-inflammatory activity by suppressing some of those cytokines in these cell lines.

Protective and curative role of vitamin D and hormones on the cadmium-induced inhibition of proliferation of human osteoblast cells.

OBJECTIVES: Exposure to cadmium (Cd), which causes environmental and industrial pollution, causes toxicity in many tissues and organs, especially bone, lung and kidney. Hormones, growth factors and other stimuli act on bone tissue through osteoblasts. In this study, it was aimed to determine the effects of Cd on hFOB1.19 osteoblast cells and the protective and healing potentials of estrogen, androgen and vitamin D against the inhibitory effect of Cd on the proliferation. METHODS: hFOB1.19 cells were cultivated in our laboratory using Dulbecco's Modified Eagle's Medium-F12, HEPES medium, containing 10% fetal bovine serum, 1% penicillin/streptomycin in 34.5 °C 5%CO2 incubator. To determine its protective potentials for the toxicity of CdCl2, it was previously applied 1,25(OH) 2D vitamin, 17ß-estradiol, and 5α-androstane for 72 h to cells. To determine their curative potential, osteoblast cells, which were previously exposed to CdCl2 for 72 h, were administered 1,25(OH) 2D vitamin, 17ß-estradiol, and 5α-androstane. Following these applications were determined proliferation by XTT analysis and, the amounts of androgen receptor, estrogen receptor, vitamin D receptor, alkaline phosphatase, osteocalcin and osteoprotegerin by ELISA analysis. RESULTS: Vitamin D has been both preventive and curative effective to increase cell proliferation, which Cd reduces. Interestingly, estrogen had a preventive effect and androgen had a curative effect. CONCLUSIONS: In addition to showing the negative effects of cadmium on the proliferation of osteoblast cells, this study provides an overview of the effects of hormone and vitamin D applications before and after Cd, and these results may serve as a guide for future studies.

Is there any association between osteoporotic vertebral fracture and vitamin K epoxide reductase complex subunit-1 polymorphism in Turkish society? A pilot study

OBJECTIVE: In this study, the relationship between osteoporotic vertebral fractures and 9041 Guanine/Adenine and 3673 Guanine/Adenine polymorphisms related to the vitamin K epoxide reductase complex subunit-1 (VKORC1) gene in postmenopausal women with osteoporosis was investigated. METHOD: DNA was isolated from blood samples collected from 150 women with postmenopausal osteoporosis. Genotyping of the two polymorphic regions (9041 Guanine/Adenine and 3673 Guanine/Adenine) in VKORC1 was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. The presence of radiographic fractures among the 150 patients was ascertained by using the Genant method. RESULT: At least one fracture was detected in 98 patients, and no fracture was observed in 52 patients on radiological images. We found no association between the 9041 Guanine/Adenine (p=0.283) and 3673 Guanine/Adenine (p=0.232) polymorphisms of the VKORC1 gene and the development of secondary postosteoporotic fractures in our study. CONCLUSION: There was no relationship between osteoporotic vertebral fracture and VKORC1 gene polymorphism in a postmenopausal Turkish population.

Effects of S1P1 and S1P3 in ER+ and ER- Breast Cancer Cells.

BACKGROUND/AIM: In this study, sphingosine-1-phosphate receptor-1 (S1P1) and S1P3 receptors were silenced to evaluate proliferation, adhesion, viability and lateral motility in estrogen receptor-negative MCF-7 and estrogen receptor-positive MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Groups of MCF-7 and MDA-MB-231 cells with: no small interfering RNA (siRNA); siRNA with no target; S1P1-silencing siRNA; S1P3-silencing siRNA; and siRNAs silencing both S1P1, and S1P3 were examined for this purpose at 24, 48 and 72 h after intervention. RESULTS: Viability of cells was reduced due to suppression of S1P1/S1P3. While no change was observed in the proliferation of MCF-7 cells, the proliferation of S1P1/S1P3-suppressed MDA-MB-231 cells was reduced. S1P1/S1P3 suppression resulted in reduction of adhesion of MCF-7 cells, but to an increase of MDA-MB-231 cells. Lateral motility was reduced in all S1P1/S1P3-suppressed groups. CONCLUSION: Silencing the receptors simultaneously rather than separately was more effective. Additionally, the different characteristics of cancer cells affected the proliferation and adhesion of cells differently. This difference may be associated with the estrogen receptors in the cells.

Efficiacy of resveratrol and quercetin after experimental spinal cord injury.

BACKGROUND: The aim of this study was to investigate the effect of natural antioxidants resveratrol and quercetin on oxidative stress and secondary cell damage in rats with acute spinal cord injury. METHODS: In this experimental study, 42 male Sprague-Dawley rats were used. Spinal cord injury was performed with clip compression method at level of T4-5. The study was conducted using 6 groups: control, trauma, trauma and solvent, trauma and resveratrol, trauma and quercetin, and trauma with combined resveratrol and quercetin. All rats were euthanized 48 hours after the procedure. Effects of resveratrol and quercetin on serum and tissue total antioxidant capacity and paraoxanase activity level were examined. RESULTS: Compared to trauma group, there was a significant increase in total antioxidant capacity and paraoxanase activity level in resveratrol, quercetin, and combined treatment groups. There was no significant difference between resveratrol and quercetin groups with regard to total antioxidant capacity and paraoxanase activity level. Total antioxidant capacity and paraoxanase activity level were significantly higher in solvent group than trauma group. In histopathological evaluation, there was a decrease in polymorphonuclear leukocyte infiltration in solvent, resveratrol, quercetin, and combined treatment groups. CONCLUSION: Biochemical and histological staining results of present study showed that resveratrol and quercetin may be effective in preventing secondary damage in spinal cord injury.

Estrogen and Androgen Hormone Levels Modulate the Expression of PIWI Interacting RNA in Prostate and Breast Cancer.

PIWI interacting RNAs (piRNAs), a member of non-coding RNA, originate from intergenic repetitive regions of the genome. piRNA expressions increase in various cancers and it is thought that this increase could be caused by hormones. We aimed to determine the effects of hormones on piRNA expression in breast and prostate cancer. High viability and a decrease in adhesion were observed at the concentrations of the highest proliferation. Furthermore, an increase in adhesion was also observed in MDA-MB-231 cells. After hormone treatment, while piR-651 expression had increased both breast and prostate cancer cell lines, piR-823 expressions increased in prostate cancer cell lines and only in the breast cancer cell line which was malignant. Thus, it was determined that piR-823 might show different expressions in different type of cancers.

[Drug carrier nanosystems in malignant pleural mesothelioma]. / Malign plevral mezotelyomada ilaç tasiyici nanosistemler.

Malignant pleural mesothelioma (MPM), the incidence increased with each passing day, is an important lethal disease due to the limited survive with available treatment methods and with the lack of a standard treatment. Response and survive rates of cytotoxic agents which is used in MPM treatment are not good enough. Therefore, treatment studies of MPM seem to quite important and urgent. In cancer therapy, convensional chemotherapeutic agent applications, due to the lack of selectivity, lead to systemic toxicity. Besides the limited solubility of the agent used, the distribution between the cells is weak. It is very difficult to the pass through cellular barriers, particularly, drug resistance may develop to the treatment. All of these reasons lead to failure in the treatment process. Because of the fact that cytotoxic drugs either kill the rapidly growing and dividing cells or make them disfunctional by showing toxic effect on them, to avoid the side effects and to make an inherent effect for cytotoxic drug of active ingredient given for treatment on tumor, different studies have been under investigation. At the present time, nanocarriers as one of these solutions seem to have an important place. Nanocarriers are promising for the development of therapeutic effectiveness and safety. It seems that use of the nanocarrier in the treatment of mesothelioma has a potential, as effective alternative a method, with improve of the drug efficacy and reduce of toxicity in normal tissues.

Impact of tannic acid on blood pressure, oxidative stress and urinary parameters in L-NNA-induced hypertensive rats.

Hypertension is a major health problem with increasing prevalence around the world. Tannic acid is water-soluble polyphenol that is present in tea, green tea, coffee, red wine, nuts, fruits and many plant foods. It has been reported to serve as an antioxidant or a pro-oxidant depending on the type of cells and its concentration. The purpose of our study was to evaluate the effect of tannic acid on systolic blood pressure, oxidative stress and some urinary parameters in the rat model of essential hypertension. Blood pressures of all rats were measured using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L-arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in order to create an animal model of hypertension. Tannic acid was intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide dismutase, catalase activity and the concentration of malondialdehyde (MDA) were determined in blood plasma and homogenates of heart, liver and kidney. In order to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid, and urea nitrogen values were measured. Compared with the hypertension group, a decrease in MDA concentrations of heart tissue (p < 0.01), urea nitrogen values (p < 0.01) and urine volumes (p < 0.001) were established in hypertension + tannic acid group. There was also a decrease in blood pressure values (20th and 30th days) of this group, but there was no a statistical difference according to hypertension group. The findings of our research show the effect of tannic acid in lowering blood pressure in hypertensive rats.

The effects of p38 gene silencing on breast cancer cells.

p38 mitogen-activated protein kinases (MAPK) are members of the MAPK family that are activated by inflammatory cytokines and a variety of environmental stresses. It mediates various biological processes. p38 MAPK activity play important roles in tumour progression. Excessive p38 expression is observed in invasive breast cancers. The aim of the present study was to investigate whether the p38 siRNA transfection of breast cancer cells is a putative preventive treatment for human breast cancer. p38 siRNA was used at a concentration of 15, 30, and 100 nM in human breast cancer cell lines (MCF-7) and normal fibroblast cell lines (NIH 3T3). After 48 and 72 h of transfection, the reduction in p38 expression was measured using quantitative real-time PCR. The activation of p38 signalling was measured by ELISA. XTT cell proliferation assay was performed to determine the effect of p38 silencing on MCF-7 and NIH 3T3 cell lines. The results demonstrated that approximately 96% gene silencing occurred by the selected siRNA targeting p38 mRNA. The most effective silencing was observed at 72 h post-transfection using 30 nM p38 siRNA. The results of ELISA showed that the expression of p38 protein was inhibited by p38 siRNA at 30 nM siRNA and 100 nM at 72 h post transfection. XTT results showed that cells stimulated by 30 nM siRNA at 72 h post transfection were the lowest in proliferation. p38 siRNA can interfere with the expression of p38 at protein level in MCF-7 cells, result in inhibition of cell proliferation. p38 siRNA may be a critical regulator to promote the proliferation and protein expression in MCF-7 cells. In this study, we demonstrate that p38 silencing is a preventive maintenance for treating breast cancer.

Relationship between plasminogen activator inhibitor type-1 (PAI-1) gene polymorphisms and osteoporosis in Turkish women

OBJECTIVE: The development of osteoporosis is associated with several risk factors, such as genetic structures that affect bone turnover and bone mass. The impact of genetic structures on osteoporosis is not known. Plasminogen activator inhibitor type-1 regulates the bone matrix and bone balance. This study assessed the correlation between plasminogen activator inhibitor type-1 gene 4G/5G polymorphisms and osteoporosis in a population of Turkish women. METHODS: A total of 195 postmenopausal female patients who were diagnosed with osteoporosis (Group I) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 90 females with no osteoporosis (Group II) were included in this study. Correlations between PAI-1 gene 4G/5G polymorphisms and osteoporosis were investigated through the identification of PAI-1 gene 4G/5G polymorphism genotypes using the polymerase chain reaction. RESULTS: No significant differences in the genotype and allele frequency of 4G/5G plasminogen activator inhibitor type-1 polymorphisms were observed between the two groups, and both groups exhibited the most frequently observed 4G5G genotype. CONCLUSION: No correlation between the development of osteoporosis in the female Turkish population and 4G/5G plasminogen activator inhibitor type-1 gene polymorphisms was observed.

Effects of various agents on DNA fragmentation and telomerase enzyme activities in adenocarcinoma cell lines.

Natural compounds such as resveratrol, tannic acid, and quercetin may help to treat cancer. Tamoxifen is a non-steroidal anti-estrogen drug widely used in the treatment of patients with estrogen receptor-positive breast cancer. The aim of the study was to compare the effects of these natural compounds and tamoxifen in colon adenocarcinoma (CaCo-2) and breast adenocarcinoma (MCF-7) cell lines, on telomerase enzyme activity, cell viability, number of cells and DNA fragmentation. In this study to determine telomerase enzyme activity was used PCR-ELISA kit. To determine cell viability and number of cells were used tripan blue stain. DNA fragmentation was determined by DNA ladder isolation kit. Tannic acid was more effective than resveratrol, with respect to reduction in telomerase activity, cell viability and cell count in breast adenocarcinoma. Tannic acid and tamoxifen was more effective than resveratrol and quercetin telomerase activity, cell viability and cell count in colon adenocarcinoma. Flavonoids such as resveratrol, tannic acid and quercetin which was studied on, has benefical effects on cancer therapy. These effects such as decreasing telomerase enzyme activity, cell viability and number of cells and inducing DNA fragmentation (apoptosis) must be studied for assist to develop new therapeutic pathways. There should be much more sudies in order to discover resveratrol, tannic acid and quercetin and other potential medicines.

Role of phenolic compounds in nitric oxide synthase activity in colon and breast adenocarcinoma.

Cancer chemopreventive agents are designed to reduce the incidence of tumorigenesis by intervening at one or more stages of carcinogenesis. This study aimed to determine the effects of resveratrol (RES) and tannic acid (TA), which are chemopreventive agents, on the nitric oxide synthase (NOS) levels that are effective for development of cancer in colon and breast cancer cell lines. The CaCo-2 (human colon carcinoma cell line) and MCF-7 (Michigan Cancer Foundation-7; human breast adenocarcinoma cell line) cells were grown in the laboratory. RES and TA were used to treat CaCo-2 and MCF-7 cells. Nitric Oxide Synthase Assay Kit was used to determine the NOS enzyme activity of CaCo-2 and MCF-7. Statistical differences between control and RES- and TA-treated cells were calculated using the Student's t-test for double comparison. It was observed that NO activity was generally decreased in CaCo-2 and MCF-7 cells, in which RES and TA were applied. Results suggest that the phenolic compounds RES and TA have different effects on NOS enzyme activity of the colon and breast cancer cells.

Digoxin may provide protection against vasospasm in subarachnoid haemorrhage.

BACKGROUND: Vasospasm is a significant reason for poor clinical outcome in subarachnoid haemorrhage (SAH). One of the possible causes of vasospasm is attributed to the inhibition of Na(+)/K(+)-ATPase and increased intracellular calcium. Although digoxin, a cardiac glycoside (CG), inhibits the Na(+)/K(+)-ATPase, diverse and contradictory biological actions of CGs have also been reported. This study aimed to investigate the effect of digoxin on an experimental vasospasm after subarachnoid haemorrhage (SAH) in rats. METHODS: The rats used in the study were divided into normal, saline, SAH, and drug groups. A double-haemorrhage method was applied for the SAH groups. Normal saline or blood samples were injected into the cisterna magna. No surgical procedures were performed on the normal group. For the drug groups, daily digoxin was administered intraperitoneally after saline or blood injections. On days 3 and 7 after injections, the brains and basilar artery sections of all the groups were prepared for light-microscopic examination. The wall thickness and luminal area of the basilar artery were calculated by using medical imaging software. RESULTS: Increased wall thickness and reduced vessel luminal area were conspicuously significant in the SAH groups which did not receive digoxin. In SAH groups after digoxin administration, the vessel wall thickness decreased, and no significant change was found in vessel wall thickness when compared with the normal and saline groups. The vessel luminal area was not reduced in SAH after digoxin administration. CONCLUSIONS: These results suggest that digoxin administration in experimental SAH may have a beneficial effect on the protection against vasospasm. If further investigations support our results, the present study may offer a new insight into the treatment of SAH.

The effects of resveratrol and tannic acid on apoptosis in colon adenocarcinoma cell line.

OBJECTIVE: To investigate the effects of resveratrol and tannic acid on apoptosis, and Bcl-2 homologous antagonist/killer (Bak) and fas associated death domain (FADD) proteins in the CaCo-2 cell line. METHODS: In the present study, resveratrol and tannic acid were administrated in the CaCo-2 cell line at doses of 25, 50, and 100 microM. The CaCo-2 cells were grown and cultured in the Medical Biology Department, Eskisehir Osmangazi University, Eskisehir, Turkey in 2007. The effects of these agents on apoptotic index were determined by Apop Taq peroxidase kit and their effects on the ratios of Bak and FADD proteins by the immunohistochemical staining method at 24, 48, and 72 hours. Stained and non-stained cells in 30 separate areas of the 3 separate chamber slides, prepared for each group, were counted. The percentage of apoptosis, and Bak and FADD proteins was calculated with the control. Mean +/- standard error values were calculated for the 3 experiments. RESULTS: Apoptotic index, Bak protein percentage ratio, and FADD protein percentage ratio values in all groups that received tannic acid and resveratrol increased when compared within the groups. This increase was found to be time and dose independent in all parameters. CONCLUSION: Cells undergo apoptosis in 2 pathways (mitochondrial and death receptor) in resveratrol and tannic acid induced CaCo-2 cells.

The effect of doxorubicin on rats that received toxic and carcinogenic benzo(a)pyrene.

Benzo(a)pyrene (B(a)P) is a polycyclic aromatic hydrocarbon with carcinogenic and toxic effects. Doxorubicin is a DNA-interacting drug widely used in chemotherapy. In the present study we investigated the effects of doxorubicin on rats that received benzo(a)pyrene. Sprague-Dawley male rats, 3-4 months old, were divided into 5 groups (n=9 per group). Group 1 (controls) received normal saline intraperitoneally (i.p.) and intragastrically (i.g.), Group 2 (controls) similarly received corn oil i.p. and i.g., Group 3 received corn oil soluble benzo(a)pyrene (10mg/kg b.wt every 10 days for 40 days), Group 4 received doxorubicin (4 mg i.p. on 3 consecutive days), Group 5 received doxorubicin for 3 days (as in group 4) followed by benzo(a)pyrene as in group 3. After twenty-four hours urine samples were collected, heart blood, liver and kidney tissue samples were obtained. Biochemical data were evaluated on urine and blood; liver and kidney tissue samples were investigated histologically. Uric acid, urine creatinine, creatine clearance, urea nitrogen, serum creatinine values, serum glutamic oxaloacetic transaminase (SGOT, AST), serum glutamic pyruvic transaminase (SGPT, ALT), alkaline phosphatase (ALP, AP), superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) levels were significantly different in the 3rd group compared with control groups. Most of the parameters group 5 were statistically similar to control values. Histological appearance of the liver and the kidney tissue samples supported the improvement in the 5th group. The result of our study indicated that liver and kidney functions impaired with benzo(a)pyrene may be partially restored by doxorubicin.