Effect of Sofosbuvir Administration and Its Withdrawal on the Submandibular Salivary Gland of Adult Male Albino Rats: A Histological and Ultra-Structural Study

BACKGROUND: Sofosbuvir (SOF) was approved in 2013 as a part of first-line treatment for hepatitis C virus (HCV); it has activity against all genotypes with extrahepatic adverse effects have recently arisen. AIM: Investigating sofosbuvir-induced alterations in the rat submandibular salivary gland (SMSG). METHODS: A group of 80 adult albino rats weighing about ± 150 gm were used in the experiment. The rats were divided into 3 groups: Group I (control group) received distilled water, Group II (experimental group) divided into 2 subgroups and received SOF 40 mg/kg/day dissolved in distilled water for 1 and 3 months and Group III (recovery group) allowed for 1 month of recovery after SOF withdrawal. All animals were sacrificed; the SMSG was dissected, and specimens were examined histologically and ultra-structurally. RESULTS: Compared to Group I, Group II subgroup (1) showed acinar and ductal vacuolisation, discontinuity of the epithelial lining associated with retained secretion and congested blood vessels. These changes were found to be exaggerated in the subgroup (2) accompanied by acinar and ductal shrinkage, interstitial oedema, haemorrhage, chronic inflammatory cells infiltration and loss of gland compactness. Amelioration of the histological changes was detected in Group III after SOF withdrawal. The ultrastructural examination confirmed these histological results. CONCLUSION: SOF had induced apparent alterations in the structure and ultrastructure of SMSG. The SOF-induced alterations were time-dependent, attributed mainly to mitochondrial toxicity and partially ameliorated by its withdrawal.