Ischemia/reperfusion (I/R) is a major cause of acute kidney injury. Several studies have shown that renin angiotensin (Ang) system and activation of Ang II type 1 receptor (AT1) are involved in various forms of kidney diseases. Likewise, Ang 1-7 as a physiologic antagonist of AT1 and losartan could possibly protect the kidney against I/R damage. Therefore, we investigated renal injury by administering the drugs before and after I/R. Fifty-four male Wistar rats were randomly assigned to five groups as follows. 1, Sham operated; 2, saline group (as a control group); 3, losartan group; 4, Ang 1-7group; and 5, Ang 1-7 + losartan simultaneously. It should be noted that groups 2-5 consisted of two separate I/R-induced subgroups both receiving medication where the first groups received the treatment 15 min before induction of I/R while the medications were given to the second groups immediately after induction of I/R. Twenty four h after I/R, blood samples were collected, and then levels of serum urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), lactate dehydrogenase (LDH) and total antioxidant capacity (TAC) were measured. Likewise, nitrite, MDA and TAC were measured in the homogenized kidney tissues. After the induction of I/R, the BUN, Cr, LDH, and kidney tissue damage score increased. Administration of Ang 1-7 alone or simultaneously with losartan decreased the levels of aforementioned factors. Also, kidney MDA and nitrate levels significantly increased after I/R induction (P < 0.05). According to the results of this study, it can be claimed that the effect of losartan in the presence of Mas receptor is statistically significant and kidney damage dramatically decreases.
Background: Nephrotoxicity is the most recognized side effect of gentamicin. Vitamin E and vitamin C demonstrate their effective role in the prevention of nephrotoxicity. Likewise, previous studies have suggested that women have low risk of end-stage renal disease at premenopausal period. Objectives: This study aims to investigate the possibility of any gender difference in response to antioxidant effects vitamins E and C in gentamicin-induced nephrotoxicity. Materials and Methods: Wistar rats were randomly assigned to 6 groups each including both male and female rats. The first and second groups received saline (control group) and almond oil, the third group received gentamicin. The fourth group received a regular dose of gentamicin + vitamin E. Similarly, the fifth group received a regular dose of gentamicin + vitamin C. The sixth group received a dose of gentamicin + vitamin C and E simultaneously constantly. This protocol continued for 9 days. Results: Gentamicin increased significantly urea, creatinine (Cr) and malondialdehyde (MDA), but it decreased superoxidase dismutase (SOD) level (P < 0.05). Treatment with antioxidant vitamins improved urea, creatinine, MDA, and SOD serum level significantly in both genders (P <0.05). Likewise, kidney MDA level enhanced significantly (P <0.05) and treatment with antioxidant vitamins reduced MDA level too (P <0.05). Gentamicin decreased kidney SOD activity in male and female rats (P <0.05). However, treatment with antioxidant vitamins did not improve its level in male rats, while in female rats, vitamins E and C compensated for kidney SOD activity. Conclusions: Antioxidant vitamins modified gentamicin-induced nephrotoxicity in both genders, with some difference in response to vitamins E and C between the genders, that was higher in female rats.
Backgrounds: The prevalence of metabolic syndrome (MetS) is increasing in developing countries that affects the liver in a variety of ways. This study was designed to investigate the protective role of eugenol on liver damage caused by fructose-induced MetS. Materials and Methods: Thirty male Wistar rats were randomly divided into five groups: 1: tap water (control), 2: fructose, 3: fructose + eugenol solvent, 4: fructose + eugenol 50 mg/kg, and 5: fructose + eugenol 100 mg/kg. At the end of the experiment, blood samples were taken for measurement fast blood glucose (FBG), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), low-density lipoprotein, high-density lipoprotein, cholesterol, and triglyceride. Results: FBG significantly increased in Group 2 compared to Group 1 (P < 0.001); however, it significantly decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). SGOT and SGPT levels significantly increased in Group 2 compared to the control group (P < 0.001). However, SGOT and SGPT levels significantly decreased in Groups 4 and 5. Malondialdehyde (MDA) and liver tissue damage score (LTDS) significantly increased in Group 2 compared with the control group (P < 0.01), whereas MDA and LTDS decreased in Groups 4 and 5 compared to Group 2 (P < 0.05). Conclusion: Eugenol may ameliorate liver damage in a rat model of fructose-induced MetS, and these protective effects may in part be mediated by improving antioxidant status and reducing oxidative stress and lipid peroxidation. It may also reduce hepatic inflammation and fat accumulation as well as fibrosis of liver cells.
Background:L-arginine is an important precursor for the formation of nitric oxide (NO). According to previous studies, NO function is related to gender. Likewise, chronic renal diseases have lower prevalence in female. Gentamicin (GM) is an aminoglycoside antibiotic. According to some studies, males are more sensitive to GM renal nephrotoxicity. This study attempts to find protective effects of L-arginine on GM nephrotoxicity in male and female rats.Methods:Male and female rats were divided into eight groups: Rats were randomly assigned to 8 groups each including both male and female rats. The first and second groups received vehicle (saline), the third and fourth groups received gentamicin (80 mg/kg), the fifth and sixth groups received L-arginine (150 mg/kg), and finally, seventh and eighth groups received gentamicin+ L- arginine. Next, 9 days after administering drugs, blood samples were collected from the heart. After making sacrifices, the level of blood urea, creatinine (Cr), nitrite, and malondialdehyde (MDA) was measured in serums. Likewise, nitrite and MDA were measured in the homogenized kidney tissue.Results:GM significantly increased serum level of urea and Cr in male and female rats (P < 0.05). However, co-administration of GM + L-arginine significantly did not decrease urea and Cr level in male rats, whereas, in female rats, they significantly reduced (P < 0.05). In response to GM, renal MDA level increased in male and female rats (P < 0.05), and in the presence of GM + L-arginine, the level of MDA significantly decreased in both genders (P < 0.05).Conclusions:L-arginine demonstrated some protective effects in female rats but did not protect against GM nephrotoxicity in male rats for unknown reasons, probably related to the effects of sex hormones which needs further studies to be confirmed.
Background: Nephrotoxicity is the most known side effect of gentamicin. In addition, renin angiotensin system (RAS) plays an important role in the pathogenesis of renal injury and nephrotoxicity. Hypomagnesaemia is other complication of gentamicin. Previous studies reported that magnesium plays an important role in cell enzymatic functions, reducing lipid peroxidation. Objectives: We investigated the role of losartan and magnesium sulfate (MgSO4 ) on gentamicin nephrotoxicity. Materials and Methods: In this study, rats randomly assigned to five groups. The first group, received saline, the second group received gentamicin 80 mg/kg/d, intraperitoneally (ip), and the third group, received a regular dose of losartan, 10 mg/kg/d + gentamicin 80 mg/kg/d. The fourth group received MgSO4 , 80 mg/kg/d + gentamicin 80 mg/kg/d. The fifth group obtained a continuous dose of gentamicin 80 mg/kg/d + losartan 10 mg/kg/d + MgSO4 80 mg/kg/d simultaneously. Nine days after administration of drugs, blood samples were collected from the heart. The level of urea, creatinine (Cr), malondialdehyde (MDA) and nitrite were measured in the animal serum and homogenized kidney tissue. Results: Gentamicin increased serum urea and Cr levels. The administration of losartan and MgSO4 lonely and combination of them, significantly reduced the levels of serum urea and Cr. Losartan alone and combination of losartan and MgSO4 compared with gentamicin, significantly decreased kidney MDA level too. Decrease of kidney nitrite level by gentamicin was compensated by the administration of losartan, MgSO4 alone or their combination. Additionally, losartan and MgSO4 alone and their combination together significantly reduced renal damage. Conclusions: The results of this study indicated that administration of losartan and MgSO4 individually and their combination decreased kidney nephrotoxicity and improved renal function. This effect is probably related to the improvement of antioxidant status and renal blood flow.
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