Methotrexate-induced intestine and nephrotoxicity attenuated by Andrographis paniculata via ameliorating oxidative stress, inflammation and apoptosis

Abstract

The therapeutical benefits of methotrexate (MTX) antifolate agents are non-negligible. However, their ability to cause severe intestinal and nephrotoxicity initiates burden on the patient’s life quality. Andrographis paniculata, “kings of bitter” with anti-inflammatory, anti-bacterial, detoxicant and anti-viral properties, is a preferred Asian medicinal plant for treating various disease ailments. Our study aims to determine the potential of aqueous leaf extract of A. paniculata (ALEAP) against MTX-induced intestinal and nephrotoxicity. Rats (n = 6) in 5 groups were allocated. Group 1 (normal control), group 2 (MTX − 20 mg/kg; i.p. single administration, 9th day), group 3 (MTX + ALEAP (500 mg/kg; p.o. for 10 days)), group 4 (MTX + Silymarin (100 mg/kg; p.o. for 10 days)) and group 5 (ALEAP alone for 10 days). The rats were assessed for significant alterations in renal markers, intestine and renal antioxidant levels, histopathology, cytokine levels (TNF-α, IL-6, IL-10), and apoptosis marker expression range (caspase 3, 8, BCL-2). ALEAP attenuates elevated renal markers; intestine and renal MDA, TNF-α, IL-6, caspase 3 & 8, and histopathological modifications. ALEAP restored intestine and renal antioxidant enzymes, IL-10, and BCL-2. The aqueous leaf extract of A. paniculata produced a significant outcome by maintaining intestine and kidney function and preventing cellular damage.

Graphical abstract