Alveolar process changes associated with administration of nucleos(t)ide analogue (sofosbuvir) in rat model

Sofosbuvir is a nucleotide compound that has proved to be among the most potent orally available antiviral treatments. Infrequent but serious adverse events have been reported with the use of oral nucleos(t)ide analogues.

Investigating sofosbuvir-induced alterations in the rat mandibular alveolar process.

In the study, 30 adult male albino rats were used and divided randomly into following groups: group 1, group 2 and group 3 (10 rats per group). Group 1 served as a control, group 2 received sofosbuvir through oral gavage at a dose of 40 mg/kg/day for 6 weeks, and group 3 was similar to group 2 but received sofosbuvir for 12 weeks. The animals were sacrificed at the end of the experiment. The mandibles were dissected and examined histologically as well as by scanning electron microscope (SEM) and energy dispersive X-ray unit (EDX).

Histologically, group 1 showed normal alveolar process. In group 2, histopathological changes occurred as bone trabeculae demonstrated obvious Howship's lacuna of osteoclasts. In group 3, bone trabeculae exhibited multiple degenerated areas as well as apparent vacuolization. Scanning electron microscopic examination revealed smooth alveolar bone architecture in group 1. On the other hand, groups 2 and 3 demonstrated irregular bone architecture with formation of multiple pores. EDX analysis demonstrated the highest calcium concentration in the control group, while the lowest was found in group 3. Statistical analysis of the EDX results revealed a statistically significant difference among the studied groups as the p-value was <0.01.

It has been concluded that sofosbuvir induced apparent alterations in the rats' alveolar bone. This effect was exaggerated in a longer period of drug administration. The sofosbuvir-induced alterations might be attributed mainly to mitochondrial toxicity. The effect had been clearly shown histologically and morphologically as well as in bone mineral (calcium) content.