HISTOMORPHOLOGICAL STUDY AND SERUM MICRO-RNA PROFILING AS BIOMARKERS OF CLINDAMYCIN-INDUCED LIVER DAMAGE IN WISTAR RATS
Abstract
Worldwide, the socio-economic and health effect of prescription non-adherence, self-medication, as well as abuse of prescribed drug dose, is astronomically huge. One of such drugs is clindamycin- hydrochloride which is an antibiotic medication used for treatment of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, pneumonia, acute otitis media (middle ear infections), and endocarditis. It is also used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus infection (MRSA). Microscopic ribonucleic acids (miRNAs) are small RNA (ribonucleic acid) molecules transcribed from genomic DNA which, do not code for protein, but can regulate an abundance of gene transcripts in health and disease. In essence, this study sought to evaluate the hepatotoxic effects of normal and abnormal doses of CLI on some molecular indicators (miRNA-122,-152,-192 and -296) of liver damage in addition to histologic changes in non-morbid Wistar rats. Twenty (20) Wistar rats of average weight (100g-120g) were used for this research. The rats were divided into four (4) groups (A-D) of five rats each. Rats in group A (Low dose) were given 0.2ml of 75mg/5ml of CLI, B (normal dose) were given 0.4ml of 75mg/5ml of CLI, C (high dose) were given 1.0ml of 75mg/5ml of CLI, D (control) were given distilled water. At the end of the experimental period, blood was collected with a non-heparinized capillary tube via ocular puncture into plain bottles for miRNA profding, and liver tissue was collected and processed following standard histological procedure and then stained for microscopy. There was an over-expression of miRNA-122, -152,-192 and -296, respectively in rats treated with normal dose of CLI as well as miRNA-152 in rats treated with low dose of CLI. Mi-RNA-122, -192 and -296 were under-expressed in rats treated with high and low dose of CLI, respectively. There was also an under-expression of miRNA-152 in rats treated with high dose of CLI. The histological changes observed in the liver of rats treated with experimental doses of CLI were wide-ranging and these include distortion of hepatic central vein, haemorrhagic congestion in central vein, hepatocyte degeneration, obliterated sinusoids, and mild necrosis. This study concludes that inappropriate use of CLI is capable of producing acute toxic effects with the potential of progressing to irreversible liver damage.
KEYWORDS: Clindamycin, hydrochloride, microRNA, histology, necrosis.
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