The protective effect of Pistacia terebinthus L. fruit and gum against isotretinoin-induced hepatic damage in rats

With the increasing pursuit of beauty in modern times, isotretinoin a vitamin A derivative widely used in the treatment of acne vulgaris has become a controversial drug due to its therapeutic benefits as well as its potential to cause liver damage, oxidative stress, and other severe side effects. This study aims to investigate the protective effects of fruit and gum extracts of Pistacia terebinthus, commonly known as "menengiç" in Turkey and naturally found in the southern and western regions of the country, against isotretinoin-induced hepatotoxicity using an experimental model. The plant material consisted of fruit collected between September and October 2023 and gum collected between November and December 2023. Specimens were recorded and preserved in the Herbarium of the Department of Biology at Van Yüzüncü Yıl University, Faculty of Education. The collected materials were shade-dried, ground using an electric mill, and extracted for 48 hours in a 70% ethanol/30% water hydrological solvent using a magnetic stirrer. Following filtration and rotary evaporation, the extracts were stored at -18°C. In the experimental study, 64 male Wistar albino rats aged 2–3 months and weighing 190–220 grams were housed under standard laboratory conditions and divided into eight groups (n = 8 per group). These groups included: control (0,9% NaCl), isotretinoin (40 mg/kg/day), silymarin (200 mg/kg/day), P. terebinthus fruit extract (200 mg/kg/day), P. terebinthus gum extract (200 mg/kg/day), and combinations of isotretinoin with each of these treatments. To evaluate liver damage induced by isotretinoin, serum and tissue samples were collected to measure ALT, AST, LDH, HDL, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and hydroxyproline levels. Histopathological and immunohistochemical staining of liver tissues was also performed. The data were analyzed using one-way analysis of variance (ANOVA) and Tukey's post-hoc tests in SPSS 26, with a significance level set at p < 0,05. This study aims to fill a gap in the literature by evaluating the protective effects of Pistacia terebinthus fruit and gum against isotretinoin-induced hepatotoxicity, offering a comparative perspective alongside silymarin and contributing to the development of new phytotherapeutic strategies. The findings revealed that isotretinoin caused oxidative stress, inflammation, and cellular damage in rat liver tissue, which was further confirmed by histopathological evaluations. In the isotretinoin-treated group, liver tissue exhibited inflammation, apoptosis, and hyperemia, indicating impaired liver function. Administration of Pistacia terebinthus fruit and gum, either alone or in combination with isotretinoin, significantly mitigated these effects and preserved histological integrity. Notably, the gum extract demonstrated greater efficacy in reducing liver damage. Biochemically, significant increases in hydroxyproline, TOS, and OSI levels, along with a decrease in TAS, were observed in the isotretinoin group. Treatment with Pistacia terebinthus improved these parameters, indicating reduced oxidative stress and hepatotoxicity. Silymarin also demonstrated a comparable hepatoprotective effect. In conclusion, Pistacia terebinthus fruit and gum possess the potential to serve as effective protective agents against isotretinoin-induced hepatotoxicity. These results suggest that the antioxidant and hepatoprotective properties of this plant could be integrated into future pharmacological treatment strategies. Keywords: Isotretinoin, Pistacia Terebinthus, Liver, Terebinth Gum, Rats