Acute Dosage With Dexrazoxane, but not Doxorubicin, Is Associated With Increased Rates of Hepatic Protein Synthesis in vivo

Abstract

An investigation was carried out into the effects of dexrazoxane and doxorubicin on hepatic protein synthesis in vivo. The protocol included 8 groups of rats and involved a pretreatment stage of 30 min followed by a treatment stage of either 2.5 or 24 h. Male Wistar rats ( 0.15-0.20 kg) were pretreated with either dexrazoxan e (100 mg/kg; 5 ml/kg) or saline (0.15 mol/l NaCl; 5 ml/kg). At 30 min after the pretreatment , rats were again injected with either doxorubicin (5 mg/kg; 10 ml/kg) or saline (0.15 mol/l NaCl; 10 ml/kg) in the treatment phase. Rats were sacri ced at either 2.5 or 24 h after the last doxorubicin or saline injection. Rate of protein synthesis were measured 10 min prior to sacri cing rats, with a ooding dose of L-[4-3 H]phenylalanine . Liver was analyzed for the protein synthetic capacity (C s , mg RNA/g protein), the fractional rate of protein synthesis (k s , %/d), and the RNA activity (k RNA mg protein/d/mg RNA). Complementary analysis included plasma albumin, total protein and activities of alkaline phosphatase , and aspartate aminotransferase . In the 2.5-h study, doxorubici n alone had no effect on any of the above variables. Dexrazoxane alone increased C s , k s and k RNA at 2.5 h. Combined dexrazoxan e doxorubicin increased hepatic C S and k s with concomitant reductions in total plasma protein. In the 24-h study, doxorubicin alone had no effect on any of the variables. Dexrazoxan e alone had no effect on either C S , k s , or k RNA but raised plasma activities of alkaline phosphatas e and aspartate aminotransferase. Combined dexrazoxan e doxorubicin increased C s and k s and decreased total plasma protein and increased plasma aspartate aminotransferas e activities at 24 h. In conclusion, there is no evidence that acutely doxorubicin per se has measurable effects on hepatic protein synthesis in vivo in an acute period. However, acutely dexrazoxan e increases hepatic protein synthesis, which may represent its putative cytotoxic effects, as indicated by raised serum activities of liver enzymes. A combination of both dexrazoxane doxorubici n appears to have a greater effect in increasing liver protein synthesis than dexrazoxan e alone.

Phoenix dactyliferaProtects against Doxorubicin-Induced Cardiotoxicity and Nephrotoxicity

“…Moreover, nephrotoxicity was also observed by several renal functional parameters which were also a contributing factor in mortality rate. Weight loss was also observed due to less food intake as the toxic effect of drugs affects the intestinal mucosa and decreases appetite by indirect action on the gastrointestinal tract by decreasing the secretion of internal hormones [31]. Improvement in body weight was measured in groups treated with PDE compared with the intoxicated one due to increased food intake and enhancement of intestinal mucosa by use of PDE as it was reported previously [32].…”

Evaluation of the in vitro antioxidant and antitumor activity of hydroalcoholic extract from Jatropha mollissima leaves in Wistar rats

“…Due to the medications’ toxic effect on the intestinal mucosa, many people found they were eating less and losing weight. That was achieved by the drugs’ indirect effect on the digestive system, lowering release of endogenous hormones and reducing hunger ( Zima et al, 2001 ). Previous reports indicated that using Jm led to increased food intake and improved intestinal mucosa, contributing to the rise in body weight compared to the intoxicated group ( El-Far et al, 2016 ).…”