Fatih Mehmet Kandemir

Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats

Abstract Gentamicin is commonly used against gram-negative microorganisms. Its therapeutic use is mainly limited by nephrotoxicity. This study was aimed at evaluating the effect of rutin on oxidative stress, inflammation, apoptosis, and autophagy in gentamicin-induced nephrotoxicity in rats. The rats were treated with saline intraperitoneally (group I), 150 mg/kg of rutin orally (group II), 80 mg/kg of gentamicin intraperitoneally for 8 d (group III), or 150 mg/kg of rutin plus 80 mg/kg of gentamicin (group IV). The serum urea, creatinine, kidney malondialdehyde (MDA), and reduced glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and protein concentration were measured, and renal histopathology analysis and immunohistochemical staining were performed. Rutin pretreatment attenuated nephrotoxicity induced by gentamicin by reducing the urea, creatinine, and MDA levels and increasing the SOD, CAT, and GPx activity, and the GSH levels. The rutin also inhibited inducible nitric oxide synthase (iNOS), cleaved caspase-3 and light chain 3B (LC3B), as evidenced by immunohistochemical staining. The present study demonstrates that rutin exhibits antioxidant, anti-inflammatory, anti-apoptotic, and anti-autophagic effects and that it attenuates gentamicin-induced nephrotoxicity in rats.

Benefical effects of lycopene against contrast medium-induced oxidative stress, inflammation, autophagy, and apoptosis in rat kidney.

Currently, the number of imaging and interventional procedures that use contrast agents (CAs) is gradually increasing. Contrast-induced nephropathy (CIN) is the most important CA-related complication. Oxidative stress plays a significant role in its pathophysiology. Lycopene (LPN) is a natural substance with strong antioxidant capacity. The present study aimed to investigate the potential preventive effects of LPN against CIN. In total, 28 male Wistar albino rats were divided into 4 groups with 7 rats in each group; the groups include normal control group, LPN only group at a dose of 4 mg/kg/day for 10 days, CIN group by administering 10 mg/kg furosemide IM + 10 mg/kg indomethacin IP + 10 ml/kg iomeprol IV following 24-h dehydration, and CIN + LPN group. There were statistically significant increase in urea, creatinine, and malondialdehyde levels (p < 0.001, for all) but a significant decrease in glutathione, superoxide dismutase, catalase, and glutathione peroxidase levels (p < 0.001, for all) in the CIN group compared with the control group. On histological examination, a significant increase of infiltrated inflammatory cells and necrotic degenerative changes were observed in the CIN group and the immunohistochemical examination revealed a significant increase in inflammation (inducible nitric oxide synthase), autophagy (LC3/B), and apoptosis (cleaved caspase 3) in the CIN group compared with the control group (p < 0.05, for all). Significant improvements in these unfavorable parameters were observed with CIN + LPN group compared with the CIN only group. In conclusion, the favorable effects of LPN as an anti-inflammatory, antiautophagic, and antiapoptotic agent in an experimental model of CIN have been demonstrated.

Evaluation of hormonal change, biochemical parameters, and histopathological status of uterus in rats exposed to 50-Hz electromagnetic field

This study investigates the effects of the electromagnetic field (EMF) resulting from the 170 kV high-voltage power lines on hormonal status, on progesterone and 17-β estradiol levels, and on morphology of the uterus and ovaries associated with biochemical parameters of adult Wistar female rats. The rats were assigned to experimental (21) and control groups (7). The rats in the experimental group were housed in a wooden barn with 7.5 m vertical distance to the power line. Groups 1, 2, and 3 were exposed continuously (24 h) to electric-electromagnetic fields (ELF-EMFs) (48.21 ± 1.58 mG) for 1, 2, and 3 months, respectively. The rats of group 4 served as the control and were placed in laboratory conditions (The average value of the ELF was 0.75 ± 0.05 V/m. The value of the EMF was calculated to be 0.48 ± 0.05 mG.). Significant (P < 0.05) decreases were determined among the groups in terms of reproductive organ weights (uterus and ovaries) and progesterone and estrogen levels in relation to the varying periods of the estrous cycle. Although marked reductions (P < 0.05) were observed among the groups in relation to plasma catalase activity, depending on exposure time, no significant differences were found in terms of glutathione and malondialdehyde levels. It is concluded that exposure to the ELF-EMFs for different time periods produced significant decreases in plasma catalase activities in the 3-month exposure groups but no effects on progesterone level, on 17-β estradiol level, or on the morphology and weight of uterus and ovaries.

The possible role of interleukin-33 as a new player in the pathogenesis of contrast-induced nephropathy in diabetic rats.

Abstract Introduction: Patients with diabetic kidney disease (DKD) are more prone to contrast-induced nephropathy (CN). Apoptosis and autophagy were found to be essential in the pathogenesis of DKD. Interleukin-33 (IL-33) is a cytokine, but its role in DKD and CN is unknown. As IL-33 is modulated by apoptosis, we aimed to determine the relationship between IL-33 apoptosis and autophagy in DKD with CN. Materials and methods: Thirty male Sprague–Dawley rats were enrolled and randomly allocated into three groups. The first group was comprised of healthy rats (HRs), whereas the other two groups were made up of diabetic rats (DRs) and diabetic rats with CN (DRs + CN). All groups except the HRs received 50 mg/kg/day of streptozotocin (STZ). The DRs + CN group was induced by administering 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. Results: We observed increased IL-33 in the kidney tissue following induction of CN in the DRs. The DRs showed moderate immunopositivity, and the DRs + CN showed severe immunopositivity for caspase-3, cleaved caspase-3, caspase-8, caspase-9, LC3B, and Beclin-1 in tubular cells and glomeruli. The DRs also showed moderate immunopositivity in tubular cells, and the DRs + CN group showed severe immunopositivity for IL-33 in tubular cells. Increased caspase-3 was found in both glomeruli and tubuli; however, we could not demonstrate IL-33 in glomeruli. This could be secondary to inactivation of IL-33 via increased caspase-3 activity. Conclusion: The release of IL-33 from necrotic cells might induce autophagy, which can further balance the effects of increased apoptosis secondary to CN in DKD.

Mitigation of paracetamol-induced reproductive damage by chrysin in male rats via reducing oxidative stress.

Paracetamol (PRC) is a nonsteroidal anti‐inflammatory drug used widely as a painkiller for various diseases and as the symptomatic flu cure in several countries worldwide. PRC toxicity may occur under conditions of the overdose usage. Chrysin (CR) is a flavonoid that is naturally present in several plants, honey and propolis. The aim of this study was to investigate the effects of CR (at the doses of 25 mg kg−1 and 50 mg kg−1) pre‐treatment over seven consecutive days against PRC‐induced reproductive toxicity in male rats. Our results showed that PRC toxicity decreased the sperm motility, and increased dead sperm rate, abnormal sperm cell rate, apoptosis and MDA levels in testicular tissues. Pre‐treatment with CR at the dose of 25 and 50 mg kg−1 for 7 days mitigated side effects of acute PRC toxicity in male reproductive system proportionally in a dose‐dependent manner. This possible protection mechanism might be dependent on the antioxidant activity of CR. In conclusion, pre‐treatment with CR at the dose of 25 and 50 mg kg−1 for 7 days can be the beneficial against PRC‐induced reproductive toxicity proportionally in a dose‐dependent manner.

Chrysin Protects Rat Kidney from Paracetamol-Induced Oxidative Stress, Inflammation, Apoptosis, and Autophagy: A Multi-Biomarker Approach

Paracetamol (PC) is a safe analgesic and antipyretic drug at therapeutic doses, and it is widely used in clinics. However, at high doses, it can induce hepatotoxicity and nephrotoxicity. Chrysin (CR) is a natural flavonoid that has biological activities that include being an antioxidant, an anti-inflammatory, and an anti-cancer agent. The main objective of this study was to investigate the efficacy of CR against PC-induced nephrotoxicity in rats. CR was given orally via feeding needle to male Sprague Dawley rats as a single daily dose of 25 or 50 mg/kg for six days. PC was administered orally via feeding needle as a single dose on the sixth day. PC caused significant glutathione depletion, lipid peroxidation, increased serum toxicity markers (serum urea and creatinine), and reductions in activities of antioxidant enzymes (superoxide dismutase — SOD, catalase — CAT, and glutathione peroxidase — GPx). The renal protective effect of CR was associated with decreasing the regulation of serum renal toxicity markers and increasing the regulation of antioxidant enzyme activities. Additionally, PC led to significant increases in the levels of inflammatory markers including tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-33 (IL-33). Furthermore, PC induced apoptotic tissue damage by increasing cysteine aspartate-specific protease-3 (caspase-3) activity and autophagic tissue damage by increasing the expression of light chain 3B (LC3B). CR therapy significantly decreased these values in rats. This study demonstrated that CR has antioxidant, anti-apoptotic, anti-inflammatory and anti-autophagic effects on PC-induced kidney toxicity in rats.

Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats

Doxorubicin (DXR) is a highly effective drug for chemotherapy. However, cardiotoxicity reduces its clinical utility in humans. The present study aimed to assess the ameliorative effect of curcumin against DXR‐induced cardiotoxicity in rats. Rats were subjected to oral treatment of curcumin (100 and 200 mg/kg body weight) for 7 days. Cardiotoxicity was induced by single intraperitoneal injection of DXR (40 mg/kg body weight) on the 5th day and the rats sacrificed on 8th day. Curcumin ameliorated DXR‐induced lipid peroxidation, glutathione depletion, decrease in antioxidant (superoxide dismutase, catalase, and glutathione peroxidase) enzyme activities, and cardiac toxicity markers (CK‐MB, LDH, and cTn‐I). Curcumin also attenuated activities of Caspase‐3, cyclooxygenase‐2, inducible nitric oxide synthase, and levels of nuclear factor kappa‐B, tumor necrosis factor‐α, and interleukin‐1β, and cardiac tissue damages that were induced by DXR. Moreover, curcumin decreased the expression of 8‐OHdG and 3,3′‐dityrosine. This study demonstrated that curcumin has a multi‐cardioprotective effect due to its antioxidant, anti‐inflammatory, and antiapoptotic properties.

Preventive effects of hesperidin on diabetic nephropathy induced by streptozotocin via modulating TGF-β1 and oxidative DNA damage

Abstract Hesperidin (HSP) is a natural bioflavonoid with active pharmacological properties. This study was conducted to investigate the hypoglycemic and antioxidant effects of HSP on streptozotocin-induced diabetic nephropathy in rats. Serum urea, creatinine and malondialdehyde levels increased in the diabetic group, while antioxidant enzyme activities decreased compared to the control group. Moreover, transforming growth factor-beta 1 level, 8-hydroxy-2′-deoxyguanosine expression and histopathological changes in renal tissue were increased in the diabetic group. On the other hand, HSP therapy significantly regulated these values in diabetic rats. Our results indicated that HSP might be helpful to protect diabetic nephropathy.

Restorative effects of Chrysin pretreatment on oxidant–antioxidant status, inflammatory cytokine production, and apoptotic and autophagic markers in acute paracetamol‐induced hepatotoxicity in rats: An experimental and biochemical study

Paracetamol (PC) is a widely used analgesic and antipyretic drug, but it leads to acute hepatotoxicity at high doses intakes. This study was aimed to investigate the effects of Chrysin (CR) on hepatotoxicity constituted at high doses of PC in rats. Rats were subjected to oral pretreatment of CR (25 and 50 mg/kg b.w.) via feeding needle for 6 days against hepatotoxicity induced by a single dose of PC (500 mg/kg b.w.) administered orally via feeding needles. Although PC increases lipid peroxidation and liver enzyme activities, it has led to reduction of antioxidant enzyme activities. PC induced inflammatory responses by increasing the levels of TNF‐α and IL‐1β. Furthermore, PC caused apoptosis and autophagy by increasing activity of Caspase‐3 and LC3B level. On the other hand, CR therapy significantly regulated these values in rats. This study demonstrated that CR possesses restorative effect against PC‐induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptotic and autophagic tissue damage.

Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in wistar rats: by modulating inflammatory cytokines, apoptosis, oxidative stress and oxidative DNA damage

Abstract Doxorubicin (DXR) is one of the most important chemotherapeutic agent. However, nephrotoxicity reduces its clinical utility in humans. The aim of the study was to investigate protective effects of curcumin (CMN) against DXR-induced nephrotoxicity. Rats were subjected to oral treatment of CMN (100 and 200 mg/kg body weight) for 7 days. Nephrotoxicity was induced by single intra peritoneal injection of DXR (40 mg/kg body weight) on the fifth day and then the experiment was terminated on the eighth day. Nephroprotective effects of CMN were associated with decrease in serum toxicity markers and increase in antioxidant enzyme activities. CMN was able to reduced the levels of inflammatory markers such as TNF-α, NF-κB, IL-1β, iNOS and COX-2 in the rats. It also reduced the expressions of apoptotic marker including caspase-3, and oxidative DNA damage marker including 8-OHdG. Collectively, these findings indicated that CMN protect against DXR-induced nephrotoxicity.