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

Overview

Journal Open Access Maced J Med Sci

Specialty General Medicine

Date 2020 Mar 14

PMID 32165960

Citations 2

Authors

Asmaa Mahmoud Abdeen

Tarik Essawy

Saher Sayed Mohammed

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Effect of Sofosbuvir on rats' ovaries and the possible protective role of vitamin E: biochemical and immunohistochemical study.

Ebrahim N, Abdalla H, Yassin N, Maghrabia A, Morsy A Anat Cell Biol. 2023; 56(4):526-537.

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The pre-conception maternal exposure to Sofosbuvir affects the mitochondrial biogenesis in prenatal fetal tissues: Experimental study on rats.

Mahmoud S, Abdel-Aziz M, Khafaga R, Hafez H, Kamel M, Shaker S Mol Med. 2023; 29(1):71.

PMID: 37280507 PMC: 10243043. DOI: 10.1186/s10020-023-00666-x.

References

Thomas D . Curing hepatitis C with pills: a step toward global control. Lancet. 2010; 376(9751):1441-2. PMC: 4083467. DOI: 10.1016/S0140-6736(10)61497-3. View

Dyson J, Hutchinson J, Harrison L, Rotimi O, Tiniakos D, Foster G . Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use. J Hepatol. 2015; 64(1):234-8. DOI: 10.1016/j.jhep.2015.07.041. View

Johnson A, Ray A, Hanes J, Suo Z, Colacino J, Anderson K . Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase. J Biol Chem. 2001; 276(44):40847-57. DOI: 10.1074/jbc.M106743200. View

Teegen E, Durr M, Maurer M, Eurich F, Vollbort A, Globke B . Evaluation of histological dynamics, kidney function and diabetes in liver transplant patients after antiviral treatment with direct-acting antivirals: Therapy of HCV-recurrence. Transpl Infect Dis. 2018; 21(1):e13020. DOI: 10.1111/tid.13020. View

Peluso I, Valencia D, Chen C, Palmery M . Antioxidant, Anti-Inflammatory, and Microbial-Modulating Activities of Nutraceuticals and Functional Foods 2018. Oxid Med Cell Longev. 2018; 2018:3824509. PMC: 6079344. DOI: 10.1155/2018/3824509. View

Holmberg K, Hoffman M . Anatomy, biogenesis and regeneration of salivary glands. Monogr Oral Sci. 2014; 24:1-13. PMC: 4048853. DOI: 10.1159/000358776. View

Sofia M . Nucleotide prodrugs for HCV therapy. Antivir Chem Chemother. 2011; 22(1):23-49. DOI: 10.3851/IMP1797. View

Feng J, Xu Y, Barauskas O, Perry J, Ahmadyar S, Stepan G . Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus. Antimicrob Agents Chemother. 2015; 60(2):806-17. PMC: 4750701. DOI: 10.1128/AAC.01922-15. View

Bergendi L, Benes L, durackova Z, Ferencik M . Chemistry, physiology and pathology of free radicals. Life Sci. 1999; 65(18-19):1865-74. DOI: 10.1016/s0024-3205(99)00439-7. View

10.

Dabrowska E, Szynaka B, Kulikowska-Karpinska E . Ultrastructural study of the submandibular gland of the rat after 6-month exposure to cadmium and zinc in drinking water. Adv Med Sci. 2007; 51:245-9. View

11.

Tal M, Sasai M, Lee H, Yordy B, Shadel G, Iwasaki A . Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci U S A. 2009; 106(8):2770-5. PMC: 2650341. DOI: 10.1073/pnas.0807694106. View

12.

Scott J . A morphometric study of age changes in the histology of the ducts of human submandibular salivary glands. Arch Oral Biol. 1977; 22(4):243-9. DOI: 10.1016/0003-9969(77)90109-1. View

13.

Sene D, Ghillani-Dalbin P, Thibault V, Guis L, Musset L, Duhaut P . Longterm course of mixed cryoglobulinemia in patients infected with hepatitis C virus. J Rheumatol. 2004; 31(11):2199-206. View

14.

Balaban R, Nemoto S, Finkel T . Mitochondria, oxidants, and aging. Cell. 2005; 120(4):483-95. DOI: 10.1016/j.cell.2005.02.001. View

15.

Jacobson I, Gordon S, Kowdley K, Yoshida E, Rodriguez-Torres M, Sulkowski M . Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013; 368(20):1867-77. DOI: 10.1056/NEJMoa1214854. View

16.

Starkov A, Wallace K . Structural determinants of fluorochemical-induced mitochondrial dysfunction. Toxicol Sci. 2002; 66(2):244-52. DOI: 10.1093/toxsci/66.2.244. View

17.

Zeng Q, Zhang J, Zhang Z, Wang L, Wang F . Sofosbuvir and ABT-450: terminator of hepatitis C virus?. World J Gastroenterol. 2013; 19(21):3199-206. PMC: 3671071. DOI: 10.3748/wjg.v19.i21.3199. View

18.

Soriano V, Vispo E, de Mendoza C, Labarga P, Fernandez-Montero J, Poveda E . Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013; 14(9):1161-70. DOI: 10.1517/14656566.2013.795543. View