Alaadin Polat

The effects of dexmedetomidine on liver ischemia–reperfusion injury in rats

BACKGROUND Ischemia-reperfusion (IR) injury of the liver may cause various types of damage to hepatic tissues. It can affect the prognosis of patients and the success of an operation. Dexmedetomidine is a selective α2 receptor agonist. We investigated whether dexmedetomidine provides protection against IR-induced liver injury in rats. METHODS Forty rats were divided equally into four groups. In group 1, the liver was manipulated after the laparotomy, and no occlusion of the vessels of the liver was performed. In group 2, once the abdomen was opened, 60 min of ischemia and 60 min of reperfusion were applied according to the segmental hepatic ischemia model. In group 3, 10 μg/kg of dexmedetomidine was injected into the peritoneal cavity 30 min before ischemia. In group 4, 100 μg/kg of dexmedetomidine was injected into the peritoneal cavity 30 min before ischemia. Further procedures in groups 3 and 4 were the same as those of group 2. After the experiment was completed, the rats were killed. Liver tissues were removed and stored until biochemical and histologic assessments were performed. RESULTS The malondialdehyde level in group 2 was higher than that of groups 1, 3, and 4 (P = 0.001, P = 0.000, and P = 0.000, respectively). Superoxide dismutase, catalase, and glutathione levels in group 2 were lower than those in group 1 (P = 0.001, P = 0.027, and P = 0.014, respectively). Superoxide dismutase and catalase levels in group 4 were higher than those in group 2 (P = 0.002 and P = 0.000, respectively). GSH levels in groups 3 and 4 were higher than those in group 2 (P = 0.049 and P = 0.006, respectively). A lower glutathione peroxidase level was detected in groups 2 and 3 than that in group 1 (P = 000). Group 4 demonstrated an increase in glutathione peroxidase levels compared with group 3 (P = 0.014). The histologic injury scores in groups 2-4 were higher than those in group 1 (P = 0.003, P = 0.002, and P = 0.001, respectively). However, the histologic injury scores were lower in groups 3 and 4 than those in group 2 (P = 0.003 and P = 0.002, respectively). CONCLUSIONS This study showed that dexmedetomidine may protect the liver against IR injury in rats.

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.

Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin-treatment

Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.

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.

Molsidomine Prevents Cisplatin-induced Hepatotoxicity

BACKGROUND AND AIMS Despite its beneficial effects, cisplatin has considerable nephrotoxic, ototoxic, neurotoxic and hepatotoxic side effects. It has been documented that reactive oxygen radical species are involved with the pathophysiology of cisplatin-induced hepatotoxicity. Molsidomine (MOL) can exert antioxidant and anti-inflammatory effects. Therefore, the current study was planned to determine the effects of cisplatin on the liver oxidant/antioxidant system and the possible protective effects of (MOL) on liver toxicity. METHODS Animals were divided into four groups as follows: (1) control; (2) MOL; (3) cisplatin and (4) MOL plus cisplatin group. Biochemical and histopathological evaluations were performed on the extracted liver tissue. Also, serum levels of serum aspartate transaminase (AST) and serum alanine transaminase (ALT) were determined. RESULTS Our results clearly indicated that liver antioxidant enzyme activities and ALT levels were significantly decreased, whereas lipid peroxidation and neutrophil accumulation were increased in the cisplatin-treated animals (5 mg/kg single dose, i.p.) compared to the control rats. MOL treatment (4 mg/kg/day, i.p.) for 3 consecutive days provided a significant protection against cisplatin-induced hazardous changes in the liver tissue. Our histopathological findings including caspase-3 activity were also in accordance with the biochemical results. CONCLUSIONS We propose that MOL acts in the liver as a potent scavenger of free radicals, anti-inflammatory and anti-apoptotic effects to prevent the toxic effects of cisplatin, both at the biochemical and histopathological levels.

Protective and Therapeutic Effect of Apocynin on Bleomycin-Induced Lung Fibrosis in Rats

We aimed to investigate the preventive and therapeutic effect of apocynin (APO) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; APO group, 20 mg/kg APO was given intraperitoneal for 29 days; BLC-1 and BLC-2 groups, a single intratracheal injection of BLC (2.5 mg/kg); APO+BLC-preventive group, 20 mg/kg APO was administered 12 h before the intratracheal BLC injection and continued for 14 days; BLC+APO-treatment group, 20 mg/kg APO was given on the 14th day after the intratracheal BLC injection and continued to sacrifice. The BLC-1 group was sacrificed on the 14th day of BLC administration to validate BLC-induced lung inflammation and fibrosis on the 14th of study initiation. All other groups were sacrificed on the 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity, total oxidant status (TOS), and oxidative stress index (OSI) were measured. An addition to the serum myeloperoxidase (MPO), the cell count and cytokines (IL-1β, IL-6, and IL-8) of bronchoalveolar lavage (BAL) fluid were assayed. BLC-provoked histological changes were significantly detected compared to the control group. APO restored these histological damages in different quantity in the treatment and prevention groups. BLC caused a significant decrease in GSH, CAT, and GPX, which were accompanied with significantly the increased MDA, TOS levels, and OSI in the lung tissue concomitant with increased levels of the cellular account and proinflammatory cytokines in the BAL fluid. Otherwise, APO administration, both before and after BLC, reversed all biochemical markers and cytokine as well as histopathological changes induced by BLC. Interestingly, APO treatment reversed MPO activity in serum increased by BLC. In this study, both protective and therapeutic effects of APO against BLC-induced lung fibrosis were demonstrated for the first time.

Influence of dihydropyridine calcium antagonist nitrendipine on benzo(a)pyrene-induced oxidative stress

The aim of this study was to investigate the influence of nitrendipine (NIT), a dihydropyridine derived calcium channel antagonist, on polycyclic aromatic hydrocarbon benzo(a)pyrene (BAP)-induced oxidative stress. Male Sprague Dawley rats (155–220 g) were divided into four groups: Control (corn oil, i.p.); BAP (200 mg/kg, i.p.), BAP + NIT (200 mg/kg, i.p. + 50 mg/kg, i.p.), and NIT (50 mg/kg, i.p.) groups. Twenty-four hours after the injection of BAP, the rats were sacrificed and blood samples, liver, lung, and brain tissues were removed to determine serum alanine transaminase (ALT), aspartate transferase (AST), and gamma-glutamyltransferase (GGT) activities and tissue thiobarbituric acid reactive substances (TBARS), glutathione (GSH), and superoxide dismutase (SOD) levels. BAP significantly elevated serum ALT and TBARS levels in all tissues. However, NIT pre-treatment protected against increasing TBARS levels in lung and brain tissues. In addition, NIT pre-treatment significantly increased SOD levels in lung and liver tissues, as well as GSH levels in the lungs, compared to the BAP group. Thus, in conclusion, further studies are required to confirm the protective effects of calcium channel blockers, especially in liver tissue.

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.

Protective Effects of Apocynin on Cisplatin-induced Hepatotoxicity in Rats

BACKGROUND AND AIMS Despite it being a highly potent antineoplastic drug, cisplatin has important toxic adverse effects limiting its use such as nephrotoxicity, neurotoxicity and ototoxicity. It is thought that cisplatin-induced hepatotoxicity is caused by oxidative stress resulting from increased reactive oxygen species (ROS). Apocynin (APO) exerts its antioxidant effect by reducing ROS production via inhibition of NADPH oxidase. The present study intended to demonstrate effects of cisplatin on hepatic pro-oxidant/antioxidant systems and to investigate protective effects of APO against cisplatin-induced hepatotoxicity. METHODS Rats were randomly assigned into four groups (n = 8 each): a) control group; b) single dose of cisplatin (5 mg/kg); c) APO group (20 mg/kg on three consecutive days; i.p.); and d) APO plus cisplatin group. Liver tissue was assessed in all groups by biochemical and histopathological means. Also, serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase levels were studied in all groups. RESULTS When cisplatin group was compared to controls, it was seen that lipid peroxidation product, total oxidant status and ALT levels were markedly increased, whereas superoxide dismutase and glutathione peroxidase levels were overtly decreased. APO therapy markedly prevented cisplatin-induced harmful changes in liver. Our histopathological findings such as central vein dilatation, perivenuler and periportal sinusoidal dilatation, parenchymal inflammation, vacuolar changes in hepatocytes, biliary duct proliferation and caspase-3 positive hepatocytes were in accordance with the biochemical changes. CONCLUSION In light of these results, it is our thought that APO has a protective role against cisplatin-induced hepatotoxicity at both biochemical and histopathological levels.

Renal Antioxidant Status in Rats with Hypertension Induced by N Sup Omega Nitro-L-Arginine Methyl Ester

Nitric oxide (NO) has a role in the etiopathogenesis of hypertension. Relaxation of vascular smooth muscles is failed when NO production is reduced leading to increased vascular peripheral resistance. N sup omega nitro-L-arginine methyl ester (L-NAME) is one of the inhibitors of NO production. The aim of this study was to investigate oxidant-antioxidant systems of renal tissue in rats with hypertension induced by L-NAME. Rats were divided into three groups: control group and study groups treated with 100 or 500 mg/l L-NAME in drinking water for 15 days. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and NO were studied in the renal tissue after hypertension induction. Arterial blood pressure was increased in both L- NAME groups. CAT activity of 500-mg L-NAME group was higher than control. GSH-Px activity of 500-mg L-NAME group was decreased compared with 100-mg ones. NO level was lower in 500-mg L-NAME group than control. MDA levels in both L-NAME groups were decreased compared with control. In conclusion, hypertension was induced with oral L-NAME treatment. Increased CAT activity was compensated with decreased GSH-Px activity in 500-mg L-NAME group. Both study groups were protected from lipid peroxidation with NO inhibition.