Vitamin E and silymarin may protct against gentamicin-induced oxidative stress and nephrotoxicity

Researchers have found in a new study that vitamin E and Silymarin show a protective effect on gentamicin-induced oxidative stress and subsequent nephrotoxicity.

Gentamicin(GN)-induced nephrotoxicity (GIN) represents complex entity with a still unclear pathogenesis. However, it is well known that this nephrotoxicity is dose-dependent and leads to functional and morphological changes in the kidney such as elevated blood urea and creatinine level in serum, declined glomerular filtration rate, edema, and acute injury in proximal tubules.

With more usage of GN, a possible connection between GN-induced renal damage, ferroptosis and the overall antioxidant status of the organism could be investigated. Moreover, due to its beneficial effects, GN is still one of the main choices as a therapeutic agent for several diseases, and the possible reduction of its side effects with the application of certain antioxidants will be of important clinical significance.

In this study, Georgiev and team investigated the physiological roles of the antioxidative substances Vitamin E and Silymarin during Gentamycin-induced nephrotoxicity. They mainly focused on the analysis of ferroptosis during this study. They provide useful in-vivo findings, not only for gentamycin-induced nephrotoxicity in general, but also for the effects of Vitamin E and Silymarin treatment. The study findings are published in journal Pharmaceuticals.

The study was conducted with adult male white mice divided into several groups (n = 6). GN nephrotoxicity was induced by the administration of GN 100–200 mg/kg i.p. for 10 days. The control group received only saline. The other groups received either Vitamin E (400 mg/kg p.o.) or Silymarin (200 mg/kg p.o.) applied alone or together with GN for the same period. After the end of the study, the animals were sacrificed, and blood and tissue samples were taken for the assessment of biochemical parameters and antioxidant status, as well as routine and specific for GPX4 histochemistry examination.

The key findings of the study are

• The experimental results indicate that GN-induced nephrotoxicity negatively modulates GPX4 activity and is associated with increased production of ROS and lipid peroxidation.

• The groups treated with antioxidants demonstrated preserved antioxidant status and better GPX4 activity.

• Study reported significantly elevated oxidative stress with accompanying increased production of ROS, decreased redox potential, increased production of cytokines, and evidence for changes in the GPX4 axis and ferroptosis in the GN-treated mice.

• Protection with vitamin E (400 mg/kg p.o.) or silymarin (200 mg/kg p.o.) recovers most of the parameters of inflammation, oxidative stress and ferroptosis.

• The results presented above suggest that inhibition of GN-induced kidney injury affects not only the survival of the cells but also improves their anti-inflammatory status and oxidative balance.

In conclusion, the inhibition of ROS production and especially the suppression of ferroptosis, could be of clinical potential and can be applied as a means of reducing the toxic effects of GN application. Vitamin E and silymarin as ferrostatins could be used as complementary agents against gentamicin-induced side effects and, in particular, its nephrotoxicity.

Reference: Georgiev, T.; Nikolova, G.; Dyakova, V.; Karamalakova, Y.; Georgieva, E.; Ananiev, J.; Ivanov, V.; Hadzhibozheva, P. Vitamin E and Silymarin Reduce Oxidative Tissue Damage during Gentamycin-Induced Nephrotoxicity. Pharmaceuticals 2023, 16, 1365. https://doi.org/10.3390/ph16101365.