Alleviation of doxorubicin-induced nephrotoxicity in breast cancer mice by using combination of green tea and moringa: Focus on antioxidant, apoptosis, inflammation, and histopathological insights

Doxorubicin (DXR)-induced nephrotoxicity remains a major concern in cancer treatment and calls for potential prevention of kidney injury. This study aims to evaluating the nephroprotective potentials of green tea and moringa used as 1% and 2% water extracts in DXR‑induced kidney damage in female Balb/C mice with breast cancer. Thirty six female Balb/C mice were divided into six groups as follows: healthy control; 4T1 cells cancer-induced; healthy mice with DXR treatment; cancer-induced with DXR treatment; cancer-induced under DOX and treated with 1% green tea and moringa combination; cancer-induced under DOX and treated with 2% green tea and moringa combination. The variables of the experiment were body weight, tumor volume, antioxidant enzyme activities (CAT, GPx, SOD), oxidative stress markers (TOS, TAC, OSI), pro-inflammatory cytokines (IL‑1, TNF‑α), and apoptosis and inflammation-related genes (BAX, BCL2, NLRP3, NFKB). Histological analysis of the kidneys was also done to check for cellular changes. DXR treatment led to a decrease in the body weight and an increase in kidney enzymes, which is an indication of kidney damage. The levels of these enzymes were significantly lowered by the combination of herbal extracts, especially at 2%, indicating nephroprotective properties. The herbal extracts brought back the antioxidant enzyme activities to normal and reduced the oxidative stress markers in the kidney through raising the CAT, GPx, and SOD and decreasing the TOS and OSI levels. Furthermore, the herbal treatment also decreased the levels of pro-inflammatory cytokines and affected the apoptosis related gene expressions; the BAX was down-regulated and BCL2 was up-regulated, which helped in increasing the cell survival and decreasing inflammation. The extracts also reduced the NLRP3/NFKB in the kidneys of DXR‑treated mice in a dose dependent manner. Based on these results, 1% and 2% mixture of green tea and moringa leaf aqueous extracts (1:1 ratio) can be considered an appropriate combination to reduce DOX‑induced nephrotoxicity and kidney injury in cancer patients.