Carnosine protects against gentamicin-induced nephrotoxicity in rats

Acute renal failure is a major complication of gentamicin, limiting use of this antibiotic in treatment of gram negative infections. Reactive oxygen species are hypothesized to be a major factor in the nephrotoxicity of gentamicin and measures controlling this oxidative damage are widely appreciated. This work was conducted to test the hypothesis that treatment with carnosine, a biological antioxidant, may prevent or ameliorate acute renal injury, using a rat model of gentamicin-induced nephrotoxicity. Male wistar albino rats were assigned to one of six treatment groups; group I [control] rats were given normal saline injections daily for 10 days; group II rats were given IM gentamicin injections, 100 mg/kg/day, for 6 days: group III, IV and V rats were given gentamicin, together with IP carnosine injections 50, 100 and 200 mg/kg/day, respectively, for 10 days starting 4 days before gentamicin injections; and group VI rats were given only carnosine 200 mg/kg/day, for 10 days. All rats were weighed before and after experimentation, and 24 hour urine volume were collected in metabolic cages. At end of study, blood samples were collected for measurement of BUN, creatinine level and creatinine clearance. Rats were then sacrificed and the kidneys were excised. The left kidneys were homogenized and used for biochemical determination of MDA, GPX and SOD, while the right kidneys were processed for histological examination and scoring of renal cortical pathology. Results showed that gentamicin produced evident nephrotoxic effects revealed by; increased kidney weight, increased urine volume, elevations of serum levels of BUN and creatinine and decreased creatinine clearance; together with increased MDA, reduced GPX and SOD in kidney tissues. Marked histological alterations were also evident in the renal cortex [acute tubular necrosis of grade 2-3]. Carnosine treatment leads to significant dose-related attenuation of nephrotoxic effects of gentamicin revealed by reduction of the elevated biochemical parameters, improved oxidative status in the kidney, and amelioration of the histological changes. It is concluded that carnosine treatment could ameliorate the severity of renal cortical necrosis induced by gentamicin and maintain a better renal function. Thus, carnosine may be a useful candidate in the combination therapy with gentamicin to limit free radical-mediated renal injury

Effects of carnosine on liver enzymes of bilharzias infested hamsters

We tested the ability of prophylactic camosine alone and in conjunction with praziquantel to overcome the disturbances of liver enzyme activities and total protein content caused by Schistosoma mansoni infestation in hamsters. The present work showed that the infection increased hexokinase, pyruvate kinase, AMP deaminase and adenosine deaminase total activities and decreased the activity of lactate dehydrogenase, succinate dehydrogenase, arginase, transaminases [OAT, AST and ALT] and liver total protein content. Prophylactic carnosine stimulated hexokinase, pyruvate kinase, succinate dehydrogenase and both deaminases. Carnosine inhibited the activity of arginase and the three transaminases, yet this inhibition was less than that caused by untreated infection. Praziquatel therapy after prophylactic carnosine treatment caused suppression of the stimulatory effects of carnosine alone on hexokinase, pyruvate kinase, succinate dehydrogenase, both deaminases and liver total protein content. With regard to arginase and the transaminases, this combined therapy decreased the inhibitory effects of infection more than camosine alone

Effect of carnosine administration on the immune response of rabbit to schistosoma mansoni antigens

In this study, sodium dodecylsulfate polyacrylamide gel electrophoresis [SDS-PAGE] separation of soluble worm antigen preparation [SWAP], cercarial antigen preparation [CAP] and soluble egg antigen [SEA] of Schistosoma mansoni showed obvious qualitative and quantitative differences. The shared polypeptides of the three stages of S. mansoni were 116, 72.768 and 32.367 kDa under reducing conditions. The different anti-sera raised in rabbits against the different stages of antigens were recognized by electro-immune transfer blotting [EITB]. Each of the three groups separated eight bands. Carnosine treatment of rabbits immunized with SWAP, CAP or SEA resulted in the disappearance of two bands in SWAP group and one band in CAP group in comparison with the non-treated immunized groups. This indicated that the carnosine modulated the immune response of rabbits against S. Mansoni antigens

Effect of carnosine on histamine release and mortality during compound 48/80-induced shock in rats

Carnosine is an endogenous dipeptide found at high concentrations in many tissues, Early studies have demonstrated a link between carnosine, free histidine and histamine synthesis following several types of physiologic stresses. However, the precise role of carnosine and histamine in the physiologic response to stress is unknown. The present work was conducted to study the effect of carnosine administration on the lethal shock induced in rats by compound 48/80, a histamine releasing agent and whether this effect was mediated by an action on mast cell histamine release, in-vitro. The in-vivo study included 6 groups of mature albino rats which received I.P. injection of either; saline, carnosine [200 mg/kg], compound 48/80 [5 mg/kg], or carnosine [50, 100 or 200 mg/kg] followed 30 mm later by compound 48/80 [5 mg/kg]. All rats were observed for 2 hours recording mortality and survival time in each group. The in-vitro study examined the effect on isolated rat mesenteric mast cells, of the following; saline, carnosine [2-16 mg/ml], compound 48/80 [1-8 ug/ml] and carnosine [2-16 mg/ml]+compound 48/80 [4 ug/ml]. Results showed that treatment with compound 48/50 [5 mg/kg] leads to 100% mortality in mature rats, while no deaths were observed in the saline and carnosine treated groups. Pretreatment with carnosine produced significant attenuation of the lethal effect of compound 48/80, with up to 67% protection in treated animals. Examination of mast cells revealed dose-dependent degranulation by compound 48/80 and insignificant changes by carnosine treatment. Addition of carnosine to compound 48/80 leads to significant inhibition of compound 48/80-induced mast cell degranulation and histamine release. It is concluded that carnosine could attenuate the lethal effect of compound 48/80-induced shock in rats and this protective effect was mediated, at least in pan, by decreasing histamine release from mast cells

Erythrocyte and serum lipids in non-insulin dependent diabetes mellitus

Fluidity of the erythrocyte membrane and its role in the biochemical and metabolic changes in diabetes mellitus had a great interest by many investigators recently. Both plasma and erythrocyte membrane total lipids, cholesterol and phospholipids were studied in 20 non- insulin dependent diabetic patients and 10 subjects matched as regards age and sex as a control group. The study showed that there was significant increase in serum total lipids, cholesterol and phospholipids. The erythrocyte membrane cholesterol and phospholipids showed significant difference between the diabetic group and the normals. Also, the cholesterol/phospholipids showed non-significant difference. These results revealed the significance of elevated cholesterol in both plasma and erythrocyte membrane in diabetes mellitus as a major factor for diminution of the membrane fluidity. Elevation of phospholipids is a compensatory mechanism against elevation of cholesterol to keep erythrocyte membrane fluidity. Failure of this compensatory mechanism will lead to increased erythrocyte membrane rigidity with its effect on its function in diabetes mellitus