Modulatory effect of bone marrow-derived stem cells against Tamoxifen induced liver injury in albino rats: A Histological, Immunohistochemical and Biochemical study

Abstract

Tamoxifen (TAM) is commonly used for breast cancer treatment. It is considered non-steroidal antiestrogen agent. Toxic hepatitis, significant hepatic steatosis, and cirrhosis have been reported to be caused by TAM. Stem cells (BM-MSCs) are used for regenerative medicine and therapy. Aim of the work: to know how BMMSCs can improve tamoxifen induced damage in the liver of female albino rats. Materials & Methods: Ten female albino rats of average 200 gm were served as a donor for stem cells. Thirty female adult albino rats of 200-240 gm were randomly divided to three equal groups (10 animals each). Group I (Control group): provided ordinary diet. Group II (tamoxifen treated group): rats were orally given TAM with a dosage 20 mg per kg body weight daily for nine weeks consecutively. Group III (TAM & BM-MSCs group): animals were given TAM with a dosage 20 mg per kg body weight daily for nine weeks consecutively as in group II then received single intraperitoneal injection of 2×106 BM-MSCs suspended in PBS per rat then scarified after another four weeks. Biochemical studies were done, and liver sections were processed for histological, immunohistochemical and electron microscopic studies. Results: Sections of the animals’ liver taking TAM showed disturbance of the normal structure, showing cytoplasmic vacuolation, leukocytic infiltration, pyknotic nuclei, dilated cisternae of rough endoplasmic and dilated blood sinusoids also excessive collagen fibers, as well as increased expression of caspase 3. The levels of liver enzymes((AST), (ALT) and (ALP)) were elevated, On the other hand, animals’ liver sections treated with TAM followed by BM-MSCs showed improvement of the disturbed structure. In conclusion, BM-MSCs revealed ameliorative effect against TAM toxicity in rats.