Ali Beytur

Beneficial effects of chrysin on the reproductive system of adult male rats.

In this study, the beneficial effect of chrysin, a natural flavonoid currently under investigation due to its important biological activities, on reproductive system of rats was investigated. Rats (n = 16) were divided randomly into two equal groups. Rats in control group were given corn oil as carrier. Chrysin was orally administered at the dose of 50 mg kg−1 per day by gavages, and it was dissolved in corn oil for 60 days. Tissue thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, antioxidant enzyme activity (CAT, SOD and GSH‐Px), sperm parameters (motility, concentration and abnormal sperm rate), reproductive organ weight (testes, epididymis, vesicula seminalis, prostate) and serum testosterone levels were determined in the rats. Our results indicated that chrysin significantly increased GSH, CAT, GSH‐Px and CuZn‐SOD levels, but did not change the formation of TBARS significantly. In addition, sperm motility, sperm concentration and serum testosterone levels significantly increased, whereas abnormal sperm rate significantly decreased with chrysin treatment. In conclusion, it is suggested that treatment with chrysin can positively affect the reproductive system in rats, and it can be used for the treatment of male infertility.

Ameliorative effects of curcumin against acute cadmium toxicity on male reproductive system in rats

The aim of the present study was to investigate the ameliorative effect of curcumin (CMN) against acute cadmium chloride (CdCl2) toxicity on male reproductive system in rats. CdCl2 is known to be a heavy metal and potential environmental pollutant. For this purpose, 28 rats were equally divided into four groups; the first group was kept as control and given distilled water and corn oil as carrier. In second and third groups, CdCl2 and CMN were administered at the dose with 1 mg kg−1 day−1 and 100 mg kg−1 for 3 days respectively. CdCl2 and CMN were given together at the same doses in the fourth group. It was determined that acute CdCl2 exposure caused a significant reproductive damage via increased oxidative stress (increased TBARS levels and decreased SOD, CAT, GPx and GSH levels), histological alterations (necrosis, oedema etc.) and spermatological damage (decreased sperm motility and sperm concentration and increased abnormal sperm rate) in male rats. However, CMN treatment partially reversed these toxic effects of CdCl2 on the reproductive system. In conclusion, our results show that acute exposure of CdCl2 may lead to infertility, and CMN could prevent and reverse hazardous effects of CdCl2 to some degree. Thus, CMN may be useful for the prevention of CdCl2‐induced reproductive damage.

Comparison of reproductive toxicity caused by cisplatin and novel platinum-N-heterocyclic carbene complex in male rats.

Cisplatin and other platinum complexes are important chemotherapeutic agents and useful in the treatment for several cancers such as prostate, ovarian and testis. However, severe side effects including reproductive toxicity of cisplatin and other platinum complex cause limitations in their clinical usage. In this context, we aimed to compare the damage in testis caused by cisplatin and a novel platinum-N-heterocyclic carbene complex (Pt-NHC). To this end, 35 Sprague-Dawley rats were divided randomly into five equal groups (n = 7 in each group). Cisplatin and Pt-NHC were intraperitoneally administered as a single dose of 5 mg/kg or 10 mg/kg, and the rats were then killed 10 days after this treatment. The testicular tissues and serum samples were taken from all rats for the determination of reproductive toxicity. The results showed that cisplatin and Pt-NHC caused toxicity on the reproductive system via increased oxidative and histological damage, decreased serum testosterone levels and negatively altered sperm characteristics in a dose-dependent manner (p < 0.05). At the same dose levels, cisplatin generally caused lower toxicity on the reproductive system compared with Pt-NHC. In conclusion, these results suggest that Pt-NHC has more toxic effects on the male reproductive system than cisplatin, and in terms of clinical usage, Pt-NHC may be unsafe compared with cisplatin.

The Protective Effects of Apocynin on Kidney Damage Caused by Renal Ischemia/Reperfusion

PURPOSE This experimental study was designed to explore the protective effect of apocynin, the NADPH-oxidase inhibitor, on kidney damage induced by ischemia/reperfusion (I/R) in a rat model. METHODS Thirty-two rats were randomly divided into a control group and three I/R groups (1-hour ischemia followed by 23-hour reperfusion). Three I/R groups were treated by apocynin (20 mg/kg, i.p.) at two different time points (before ischemia and during ischemia). The histopathological findings, including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GPX), reduced glutathione (GSH), myeloperoxidase (MPO), blood urea nitrogen (BUN), and serum creatinine (Cr) levels, were determined. RESULTS Kidney tissue MDA and MPO, and serum BUN and Cr levels were found to be significantly higher in the I/R group, but there was no statistically significant difference in the levels of SOD, CAT, GPX, and GSH between the I/R and the control groups. Although apocynin significantly reduced MDA and MPO in group 3 and increased GPX in both treatment groups when compared to the I/R group, the elevated BUN and Cr levels were significantly reduced in treatment groups. Renal I/R injury also induced extensive tubular necrosis, glomerular damage, and apoptosis in the histological evaluation. Apocynin, especially when used during ischemia, ameliorated these histological damages in different amounts in treatment groups. CONCLUSION The beneficial effects of apocynin on renal I/R injury were evaluated for the first time.

Ameliorating effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced nephrotoxicity in rats

The aim of this study is to investigate the beneficial effects of the quercetin (Q) and chrysin (CH) against nephrotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent environmental contaminant, in rats. Rats were divided randomly into six equal groups. TCDD, Q and CH were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, 20 mg/kg/day and 50 mg/kg/day, respectively. The kidney samples were taken from all rats on day 60 for the determination of thiobarbituric acid reactive substances (TBARS), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels by spectrophotometric method. The results indicated that TCDD significantly induced lipid peroxidation and reduced antioxidant activities in rats. In contrast, Q and CH significantly prevented toxic effects of TCDD via increased GSH, CAT, GPx and SOD levels but decreased formation of TBARS. Also, it was determined that exposure to TCDD leads to significant histological damage in kidney tissue, and these effects can be eliminated with Q and CH treatment. In conclusion, the current study showed that exposure to TCDD can exert nephrotoxicity in rats. When Q and CH were given together with TCDD, they prevented nephrotoxic effects of TCDD. Their preventive effect lends more support to the role of oxidative and histological damage in the overall toxicity of TCDD.

Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Renal Injury in Rats

Background/Aims: This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Methods: Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Results: Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. Conclusion: In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time.

The effects of intracerebroventricular infusion of apelin-13 on reproductive function in male rats

Apelin is a novel bioactive peptide as the endogenous ligand for APJ. Apelin and APJ have also been identified in the testis, hypothalamic nuclei such as arcuate, supraoptic and paraventricular nuclei, implicating roles in the control of reproduction. Therefore, the present study was designed to investigate the effects of chronic central infusion of apelin-13 on LH, FSH and testosterone levels and testis morphology. 21 Wistar-Albino male rats received continuous intracerebroventricular infusion via Alzet osmotic mini pumps filled artificial cerebrospinal fluid (vehicle) or apelin-13 at concentrations of 1 or 10 nmol (10 μl/h) for seven days. At the last 90 min of the infusion period, the blood samples were collected at 15 min intervals (0-90 min) for LH and FSH analyses. At the last sampling point, the blood samples were analyzed for testosterone levels. Infusion of high dose apelin-13 significantly suppressed LH release compared with the vehicle values at 30, 60 and 75 min (p<0.05). However, FSH levels did not significantly differ among the groups. Serum testosterone levels in high dose apelin-13 group were statistically lower than the control group (p<0.05). In addition, histological examination showed that infusion of high dose apelin-13 significantly decreased the number of Leydig cells compared with the control and lower dose apelin-13 groups (p<0.05, p<0.01). Our results suggest that apelin-13 may play a role in the central regulation and decreases testosterone release by suppressing LH secretion. Thus, antagonists of the apelin receptor may, therefore, be useful for pharmaceuticals in the treatment of infertility.

Quercetin prevents docetaxel-induced testicular damage in rats

The protective effect of quercetin on docetaxel – an anticancer agent – induced testicular damage in rats was investigated. Thirty‐two rats were randomly divided into four groups: group 1 – control, carrier solutions were given; group 2 – quarcetin 20 mg kg−1 day−1 was given orally; group 3 – docetaxel 5 mg kg−1 was given intraperitoneally as single dose; group 4 – docetaxel and quarcetin were given together. The histopathological changes; the specific biochemical markers, including antioxidants; and the sperm characteristics were evaluated. Docetaxel caused a significant increase in TBARS level and a significant decrease in SOD, GPX, CAT and GSH levels in the testicular tissues compared with the control group, whereas quercetin led to a significant decrease in lipid peroxidation, which was caused by docetaxel, via reducing TBARS level and increasing the levels of SOD, CAT, GPX and GSH. In addition, after docetaxel administration, sperm motility, sperm concentration, testicular and epididymis weights were significantly decreased and abnormal sperm rate and histopathological changes were increased. However, these effects of docetaxel on sperm parameters, histological changes and the tissue weights were eliminated by quercetin treatment. Our results show that the administration of docetaxel induced the testicular damage (oxidative stress, testes tissue damage and sperm parameters), and quercetin prevented docetaxel‐induced testicular damage in rats.

Dose-dependent protective effect of ivabradine against ischemia-reperfusion-induced renal injury in rats.

Background/Aims: This study was designed to investigate the dose-dependent protective effect of ivabradine, a specific inhibitor of the cardiac sinoatrial node, on renal ischemia-reperfusion (I/R) injury in rats. Methods: Rats were divided into six groups: group 1, control; group 2, I/R (60 min ischemia followed by 24 h reperfusion); groups 3 and 4, 0.6–6 mg/kg ivabradine; and groups 5 and 6, sham+0.6–6 mg/kg ivabradine. At the end of the study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase contents were assayed in the kidney tissues; serum blood levels of urea nitrogen (BUN), creatinine (Cr) and albumin also were determined. Results: Tissue MDA levels were found to be significantly higher in the I/R group, whereas SOD and CAT levels were lower when compared to the control group. Ivabradine (0.6 mg/kg) treatment reduced the MDA levels and elevated the SOD and CAT enzyme activity. Treatment with a dose of 6 mg/kg ivabradine further increased MDA levels and did not ameliorate SOD or CAT activities. Serum levels of BUN and Cr were significantly higher in the I/R group. I/R+0.6 mg ivabradine reduced the elevated BUN and Cr levels. Conclusion: This study indicates that ivabradine exerts a dose-dependent response beyond heart rate reduction against renal I/R injury.

Evaluation of reproductive toxicity in male rats treated with novel synthesized ruthenium(II) and gold(I)-NHC complexes

In this study, we aimed to determine the reproductive toxicity in rat induced by ruthenium(II)-NHC (RuII) and gold(I)-NHC (AuI) complexes that have anticarcinogenic effects. For this purpose, 35 Sprague–Dawley rats were randomly divided into 5 equal groups. In control group, rats treated with saline, RuII, and AuI complexes were intraperitoneally given high (10 mg/kg) and low (5 mg/kg) doses to rats via a one-time administration. The animals were sacrificed, and testis tissues were taken on Day 10 of the drug administration for the determination of the biochemical, histopathological, spermatological, and hormonal parameters. It was determined that treatment group that was subjected to treatment using both RuII and AuI complexes significantly caused oxidative, histopathological, spermatological, and hormonal damage compared to control group. However, the sexual and accessory organ weight did not significantly change when compared to control. In addition, it was shown that AuI treatment generally caused more adverse effects than RuII treatment in a dose-dependent manner. In conclusion, when these synthesized compounds are used for the treatment of cancer, they could cause toxic effects on male reproductive system and lead to infertility. However, RuII complex is a more preferable option in cancer treatment, particularly in terms of user safety.