Histochemical and Immunohistochemical Evaluation of Possible Protective and Therapeutic Effects of Fluvastatin in the Rat Model of Doxorubicin-Induced Nephrotoxicity and Cardiotoxicity.
Project no. 161 · Status: Kapanmış · 2018
Summary
Doxorubicin (DOX), which was first used in the clinic in 1967, is an anthracycline antibiotic still used in the treatment of solid tumors and hematological malignancies. The use of doxorubicin, which has a mutagenic, carcinogenic and teratogenic effects as well as anti-neoplastic properties, is restricted due to acute and chronic side effects that occur in organs such as the heart, kidney, liver, brain and testicles. Statins are the most effective cholesterol-lowering agents that act by competitively inhibiting hydroxyl-methyl glutalyl coenzyme A (HMG-CoA) reductase, the key enzyme for cholesterol biosynthesis. Fluvastatin, a fully synthetic statin, inhibits HMG-CoA reductase, preventing the conversion of HMG-CoA to mevalonate (the precursor molecule of many sterols, including cholesterol). In addition to its cholesterol-lowering effect, it has been demonstrated that fluvastatin, which has been found to have antioxidant effects by cleaning hydroxyl and superoxide radicals, may play a protective role in the doxorubic-induced testicular toxicity by acting on the mTOR signal pathway. Our aim in this study was to demonstrate the possible protective and therapeutic effects of fluvastatin in doxorubicin-induced cardiotoxicity and nephrotoxicity by evaluating histochemical, immunohistochemical and Real-Time PCR analyzes. The data we obtained from our analysis revealed that doxorubicin-induced cardiotoxicity and nephrotoxicity can have both protective and therapeutic effects by regulating eNOS, iNOS, NF-?B and caspase 3 protein and mRNA expressions. However, the prophylactic use of fluvastatin has been observed to yield more positive results than for therapeutic use. Keywords: Doxorubicin, Fluvastatin, Heart, Kidney, RT-PCR