The Potential Protective Effect of L-Ascorbic Acid against Chlorambucil Induced Hepatorenal Toxicity in Adults Male Albino Rats

The high incidence of neoplastic diseases have led to manifacturing of many antineoplastic drugs to combat these diseases. Treatment with chloambucil in high dose is associated with toxicities to many organs. The aim of this study is to investigate the protective role of L-ascorbic acid for prevention of chlorambucil induced hepatic and renal toxicities in rats. Methods: This study was conducted on 160 adult male albino rats divided into 8 equal groups . Group: I rats surved as negative control. Group II received L-ascorbic acid in an oral dose of 100mg/kg/day . Group III received chlorambucil in an oral dose of 0.2mg/kg/day for 5 consecutive days .Group IV received chlorambucil in the same dose for 10 days. Group V received chlorambucil in the same dose for 15 days. Group VI recieved chlorambucil and L-ascorbic acid in oral doses of 100mg/kg/day,0.2mg/kg/day respectively for 5 days. Group VII recieved chlorambucil and L-ascorbic acid in the same doses for 10 days. Group VIII recieved chlorambucil and L-ascorbic acid in the same doses for 15 days Results: There was significant difference in mean values of serum ALT ,AST, bilirubin, createnine, blood urea nitrogen and hepatic and renal GSH in groups III,IV and V compared to group I .Also, groups VI,VII and VIII  showed  significant difference in all studied parameters compared to group Iand when groups VI,VII and VIII were compared with groups III,IV and V respectively, significant difference was also found. Histopathological examinationof liver revealed severe damage in the form of congested dilated central veins and portal tracts ,vaculated hepatocytes and pyknotic nuclei in groupIII, these changes were more obvious in  groups IV and V, the later revealed also mononuclear cellular infiltration.While there was mild damage in the form of mild congestion of the portal vein in group VI , dilated non congested portal veins in group VII and congestion of  some central veins and some portal tracts with some hepatocytes with pyknotic nuclei in group VIII. Histopathological examinationof kidneys revealed severe damage in the form of vacuolations of some renal tubules with some pyknotic nuclei in group III, loss of normal architecture of renal tubules in group IV and congested peritubular capillaries and frequently dilatated tubular lumen in group V.  On the other hand,there was mild damage in the form of few tubular cells  with pyknotic nucleiin group VI, vacuolations of some renal tubular cells in group VII and only  congestion of peritubular capillaries in group VIII. while the percentage of pathological changes in liver and kidneys were insignificantly decreased in groups VI ,VII and VIII when compared with group I. Conclusion: Chlorambucil produced significant hepatorenal toxicities in time dependent manner. Co administration of L-ascorbic acid improved such toxicities. This study was compared with other studies with larger number of experimental animals, using other antioxidants and affecting other organs. Recommendations: It is recommended to use L-ascorbic acid during therapy with chlorambucil in 5 days regimen and further studies about combined use of many antioxidants especially during prolonged therapy with chlorambucil are required.