Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats.

Since some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the protective effects of garlic (Allium sativum) were investigated in the blood and heart of streptozotocin-induced diabetic rats. Twenty-eight male Wistar rats were randomly divided into four groups: control, garlic, diabetic, and diabetic+garlic. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (50 mg/kg) in male rats. Rats were fed with raw fresh garlic homogenate (250 mg/kg) six days a week by gavage for a period of 6 weeks. At the end of the 6th week blood samples and heart tissues were collected and used for determination of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and histological evaluation. Induction of diabetes increased MDA levels in blood and homogenates of heart. In diabetic rats treated with garlic, MDA levels decreased in blood and heart homogenates. Treatment of diabetic rats with garlic increased SOD, GPX and CAT in blood and heart homogenates. Histopathological finding of the myocardial tissue confirmed a protective role for garlic in diabetic rats. Thus, the present study reveals that garlic may effectively modulate antioxidants status in the blood and heart of streptozotocin induced-diabetic rats.

Hepatic changes during various periods of reperfusion after induction of renal ischemia in rats.

BACKGROUND: Recent studies have suggested that ischemic damage to the kidneys causes liver tissue alterations. Thus, the morbidity and mortality in patients with acute renal failure (ARF) may be related to liver complications as well as to renal injury. The aim of the present study was to assess the hepatic changes during various periods of reperfusion after induction of renal ischemia. METHODS: Forty male rats were subjected to either a sham operation or to a 45-minute ischemia followed by 1, 3, 6, or 24 hours of reperfusion. Arterial pressure was continuously monitored. Blood samples were drawn to measure serum creatinine and blood urea nitrogen (BUN). RESULTS: We evaluated hepatic concentrations of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha. Ischemia reperfusion (IR) caused significant reductions in renal function as demonstrated by increased values of serum creatinine and BUN. These rats also showed significant increases in hepatic TNF-alpha and IL-10 concentrations. The most significant changes among inflammatory factors in the liver were observed at 3 hours of reperfusion: TNF-alpha, 616 +/- 41 vs 215 +/- 16, and IL-10, 926 +/- 73 vs 125 +/- 34, pg/100 mg tissue (P

Antioxidant vitamins preserve superoxide dismutase activities in gentamicin-induced nephrotoxicity.

OBJECTIVE: The clinical use of gentamicin (G) is limited due to its known nephrotoxic actions. Generation of reactive oxygen species has been proposed as a causative factor of cell death in G-induced acute renal failure (ARF). Previous studies using superoxide dismutase (SOD) mimetics have indirectly suggested a role for the superoxide ion in G-induced ARF. In this study, we directly measured the enzyme activities using in situ isolated kidneys seeking to investigate the effects of antioxidant therapy on preservation of endogenous antioxidant levels in ARF. METHODS: Thirty-five male Sprague-Dawley rats were randomly assigned to 5 groups: control, Tyrode-perfused; G, gentamicin (200 mg/L) added to the perfusate; G + vitamin E (Vit E; 100 mg/100 g BW, IM); G + vitamin C (Vit C) added to the drinking water for 3 days (200 mg/L) and to the perfusate (100 mg/L); G + Vit E + Vit C. SOD activities were determined in renal tissues based on NAPDH oxidation at 340 nm by spectrophotometry. RESULTS: SOD activity was significantly reduced in the G group compared with the controls (P<.05). Administration of Vit E alone or in combination with Vit C significantly preserved enzyme activity levels compared with the G group (P<.05). CONCLUSION: Antioxidant vitamins have a role in preservation of renal endogenous antioxidant activities, namely SOD, in G-induced nephrotoxicity.

Cyclosporine effects on the antioxidant capacity of rat renal tissues.

OBJECTIVE: Cyclosporine (CsA) has been shown to improve long-term survival after organ transplantation. However, CsA therapy is associated with a variety of side effects, among which nephropathy is the major one. Recent studies have suggested increased oxidative stress as a cause of drug nephrotoxicity. Therefore, this study was designed to evaluate the effects of CsA administration on the antioxidant capacity of kidney tissue. METHODS: Adult male Sprague-Dawley rats were randomly assigned into 2 groups: one group received CsA (25 mg/kg/d, IP for 2 weeks) and a control group (no CsA administration). After 2 weeks, the kidneys of the rats from both groups were removed under anesthesia. A 50 mg fresh kidney tissue sample was homogenized in ice-cold phosphate buffer. Total antioxidant capacity (Ferric Reducing Ability of Plasma [FRAP]) in the homogenates was assayed based on the Benzie spectrophotometric method. RESULTS: FRAP in the kidney tissues had been significantly decreased by 2 weeks of CsA administration when compared with control rats (P<.05). CONCLUSIONS: These data suggested that CsA administration may decrease the antioxidant capacity of renal tissues. More studies on the evaluation of the protective effects of antioxidant therapy against CsA nephrotoxicity are underway.

Acid-base status determines cyclosporine-induced hypercalciuria.

OBJECTIVE: Cyclosporine (CsA) causes tubular dysfunction characterized by polyuria, calcium wasting, distal tubular acidosis, and hyperkalemia. The hypercalciuria induced by CsA administration is associated with an inhibition of calbindin D(28k) expression. It has also been shown that chronic metabolic alkalosis increased the expression of Ca(2+) transport proteins accompanied by diminished urine Ca(2+) excretion. The aim of this study, therefore, was to determine the effect of acid-base status on CsA-induced hypercalciuria. METHODS: Experiments were performed on male Sprague-Dawley rats. Metabolic alkalosis and acidosis were induced respectively by adding 0.28 mol/L NaHCO(3) and 0.28 mol/L NH(4)Cl in the drinking water for 7 days; control rats received regular tap water. Seven days after NaHCO(3) or NH(4)Cl administration, rats were treated with CsA (25 mg/kg, IP) daily for 14 days. To estimate glomerular filtration rate (GFR) over time, animals were placed in metabolic cages. Fractional urinary calcium excretion was determined by standard formula. RESULTS: The CsA group showed decreased serum calcium and increased fractional urinary calcium excretion compared with the control group. Creatinine clearance was also significantly reduced. Metabolic alkalosis alone did not affect GFR, but significantly prevented an increase in fractional urinary calcium excretion induced by CsA, whereas chronic metabolic acidosis resulted in the exact opposite effect. CONCLUSIONS: It is essential for nephrologists to fully understand the mechanisms of CsA-induced renal injury. In this study, metabolic alkalosis reduced CsA-induced hypercalciuria. Further studies are needed to elucidate whether this effect may be achieved pharmacologically by the expression of Ca(2+) transport proteins.

Comparative effects of selective and non-selective nitric oxide synthase inhibition in gentamicin-induced rat nephrotoxicity.

Different nitric oxide synthase (NOS) isoforms are found in the kidney. Some studies provided evidences that increased endothelial NOS (eNOS) activity leads to restoration of renal function after injury, but activation of inducible NOS (iNOS) aggravates renal failure. In the present study, the beneficial effects of selective iNOS blockade in gentamicin (GM) induced nephrotoxicity have been investigated. Four groups of rats were studied. Untreated control rats received saline. In GM group, GM was injected (IV, 4 mg kg(-1)). In GM + L-NAME group rats received L-NAME (N-omega-L-arginine methyl ester, a non-selective NOS inhibitor) simultaneously with GM (IV, 30 mg kg(-1)). Additional doses of L-NAME were administered 2 and 4 h after GM (IP, 30 mg kg(-1)). In GM + L-NIL group rats were treated by N-imino-ethyl lysine (L-NIL, a selective iNOS inhibitor). First dose (IV, 3 mg kg(-1)) administrated simultaneously with GM. Next doses (IP, 3 mg kg(-1)) were administered 2 and 4 h after GM. In all groups, serum and urine creatinine levels were measured. Creatinine clearance was calculated and considered as an estimation of glomerular filtration rate (GFR). Urine N-acetyl-b-D-glucose aminidase (NAG) activities were also determined. After experiments, kidney sections were histologically studied. Selective iNOS inhibition by L-NIL prevented the GM-induced decrease in GFR and increase in creatinine levels, while complete non-selective NOS inhibition by L-NAME aggravated the GFR reduction, elevation of creatinine levels and enzyme release (P < 0.05). Histological studies showed that GM-treated kidneys had evidences of tubular damages and these damages were less evident by the administration of L-NIL. In conclusion, selective inhibition of iNOS may prevent GM-induced nephrotoxicity, whereas non-selective inhibition of NOS aggravates it.