Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties

Abstract

Silymarin (SLY) and naringin (NRG) are natural flavonoids that have been reported to have many benefits and medicinal properties. The present study was designed to investigate the protective effect of SLY and NRG against methotrexate (MTX)‐induced nephrotoxicity in experimental animals. Rats were subjected to oral pretreatment of SLY (25 and 50 mg/kg body weight (b.w.)/day) and NRG (50 and 100 mg/kg b.w./day) for 7 days against renal toxicity induced by single intraperitoneal administration of MTX (20 mg/kg b.w.). MTX resulted in an increase in serum toxicity markers, lipid peroxidation, and reduction in activities of antioxidant enzymes. Additionally, MTX provoked inflammatory responses by increasing the levels of TNF‐α, IL‐1β, IL‐6, NF‐κB, and activation of COX‐2 and iNOS. Furthermore, MTX administration caused apoptosis and autophagy by increasing activity of Caspase‐3 and light chain 3B level. Conversely, SLY and NRG therapy significantly decreased these values in rats. This study demonstrated that SLY and NRG protect against MTX‐induced nephrotoxicity. Practical applications Chemotherapeutic drugs have been used for cancer treatment for many years. However, in the treatment process, they may damage organs such as liver and kidney, prolong the treatment process and negatively affects patient welfare. This study revealed that silymarin and naringin exhibited potent anti‐inflammatory, antiapoptotic, and antiautophagic effect in renal injury caused by methotrexate, a chemotherapeutic drug. Therefore, treatment silymarin and naringin can be used for the beneficial effect against methotrexate‐induced kidney damage in cancer chemotherapy.

Moringa oleiferaseed oil or virgin coconut oil supplementation abrogates cerebral neurotoxicity induced by antineoplastic agent methotrexate by suppression of oxidative stress and neuro‐inflammation in rats

“…Methotrexate (MTX) is an antineoplastic drug widely applied in the treatment of cancers and non‐cancerous diseases like rheumatoid arthritis and psoariasis (Kandemir et al, ). MTX inhibits enzymatic incorporation of reduced folate into nucleotide synthesis, thus inhibiting DNA synthesis.…”

“…Studies show that MTX enhances free radical production in brain tissue to decrease antioxidant defense system leading to oxidative stress and MTX‐induced neurotoxicity (Uzar et al, ). However, recent investigations have associated MTX‐induced oxidative stress to inflammatory cascades via increased levels of cytokines and nuclear factor‐ĸB expression in renal tissue (Kandemir et al, ; Rashid et al, ). Brain is vulnerable to oxidative injury because of its low antioxidant defenses, high‐energy demand and saturated fatty acids (Soni, Prakash, Dabur, & Kumar, ).…”

The effects of hesperidin on sodium arsenite-induced different organ toxicity in rats on metabolic enzymes as antidiabetic and anticholinergics potentials: A biochemical approach

“…Lipid peroxidations are responsible for the various diseases, such as atherosclerosis, aging, radiation injury, cancer, and inflammation (Alim & Beydemir, ). Several in vitro studies have reported that polyphenols have important radical scavenging features (Caglayan, Temel, Kandemir, Yildirim, & Kucukler, ; Kandemir, Kucukler, Caglayan, et al, ). Also, a number of studies have determined that polyphenols play role inhibit LDL oxidation, which is a significant factor in the onset of coronary heart disease and atherosclerosis.…”

“…Orange juice includes flavonoids related to antioxidant activity. Naringin (Kandemir, Kucukler, Caglayan, et al, ) and hesperidin (Ekinci Akdemir et al, ) are glycosides and primarily report to the protective and antioxidant activities. They found in orange peel and play a key role against damaging biological oxidative stress (Kanaze et al, ) PON1, an anti‐inflammatory and antioxidant enzyme found in the liver.…”

Protective effects of quercetin against brain injury in a rat model of lipopolysaccharide‐induced fetal brain injury

“…Inflammation is a cellular response frequently induced by oxidative stress stimulation (Gill et al, 2010; Kandemir et al, 2017a,b). It is critically involved in both normal brain development and injury during embryogenesis.…”