HISTOPATHOLOGICAL TOXICITY OF DIAZEPAM: AN IN-DEPTH REVIEW

Abstract

Background -Diazepam is a primary drug for treating neurological diseases, muscle spasms, and alcohol withdrawalsymptoms. People usually evaluate and use the sedative effect of the drug on their own without prescription or supervision. Surprisingly, the effect of diazepam on tissue organs is relatively scarce compared to its well-documented pharmacological efficacy. It’s on this background that the present study was carried out. This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR). Most studies on benzodiazepine- induced toxicity were based on case reports, case series, or retrospective analyses, which often lack the rigor of controlled clinical trials. However, Diazepam of 5 mg / kg body weight was characterized as a high dose in experimental animals. The liver often cannot metabolize the entire amount of the applied diazepam and thus accumulates it on prolong use. Histopathological analysis of the liver, kidney, spleen, and thymus treated with diazepam showed markedly thickened capsules and disorganization of cells. There were increased interstitial gaps in the lungs and kidney parenchyma, and abnormal intercalated discs in the cardiac muscles. Intra- sinusoidal macrophages and many cells with karyolitic nuclei were also seen in the kidney. In addition to the increase in the number of hepatocytes and increase in their mitotic index, the number in apoptosis in treated animals organs is also increased. As with any medication, individual patient factors, such as preexisting renal impairment or concurrent use of other drugs, may increase the risk of adverse effects.