Hepatorenal protective effects of protocatechuic acid in rats administered with anticancer drug methotrexate

Abstract

<jats:p> The efficacy of methotrexate (MTX) as an anticancer drug is limited by some adverse effects including hepatic and renal toxicities. The present study investigated the possible protective effect of protocatechuic acid (PCA), a phenolic phytochemical widely present in several edible vegetables and fruits, on hepatorenal toxicity associated with MTX treatment in rats. Male Wistar rats were randomly assigned to five groups ( n = 10), namely control, MTX alone (20 mg/kg), PCA alone (50 mg/kg), and rats that were coadministered MTX and PCA at 25 and 50 mg/kg. The MTX was administered as a single intraperitoneal dose on the first day, whereas PCA treatment lasted 7 days. Results indicated that PCA significantly ( p &lt; 0.05) abrogated MTX-mediated elevation in indices of hepatorenal toxicity. Furthermore, PCA protected against MTX-induced decreases in glutathione level and antioxidant enzyme activities as well as the increase in reactive oxygen and nitrogen species and lipid peroxidation in the liver and kidney of the treated rats. Administration of PCA markedly abated MTX-induced increases in interleukin-1β, tumor necrosis factor alpha, and caspase 3 activity in the rats. The biochemical data on the hepatorenal protective effects of PCA were well supported by the histological data. Collectively, PCA protected against MTX-induced hepatorenal toxicity via antioxidant, anti-inflammatory, and antiapoptotic mechanisms. </jats:p>

Protocatechuic acid attenuates lipopolysaccharide‐induced septic lung injury in mice: The possible role through suppressing oxidative stress, inflammation and apoptosis

“…Previous investigations found that PCA inhibited lipid peroxidation under different conditions, such as renal damage following doxorubicin treatment (Molehin et al, 2019) and murine diabetic model (Adedara et al, 2019). PCA exerts its antioxidant properties through mitigation of free radicals, activation of the Nrf-2 pathway, and reinforcement of GSH and its dependent enzyme activities (Cheng et al, 2019;Owumi, Ajijola, et al, 2019;Owumi, Ochaoga, et al, 2019). In addition, the phenolic hydroxyl groups present in PCA are correlated to the activation of endogenous antioxidant enzymes (Han et al, 2018).…”

“…Previous studies using different animal models have demonstrated the anti-inflammatory potential of PCA (Al Olayan et al, 2020;Owumi, Ajijola, et al, 2019;Owumi, Ochaoga, et al, 2019). In addition, Wang et al (2015) showed that PCA treatment blocks NF-κB activation through enhancement of peroxisome proliferator-activated receptor-gamma in human gingival fibroblasts.…”

Rutin ameliorates copper sulfate‐induced brain damage via antioxidative and anti‐inflammatory activities in rats

“…The chemoprotective effect of various polyphenolic compounds has been widely reported [ 29‐33 ] against cellular injury. Polyphenol confers protective benefits against chemical damage to cells, [ 34‐36 ] disease onsets such as cancer, [ 37,38 ] and neurological syndromes.…”

N ‐acetyl cysteine co‐treatment abates perfluorooctanoic acid‐induced reproductive toxicity in male rats

“…The activities of testicular and epididymal myeloperoxidase (MPO) were evaluated by the modified method described by Trush et al., and as previously reported (Owumi et al., 2019; Trush et al., 1994), MPO catalyses the oxidation of O ‐dianisidine in the presence of H 2 O 2 to yield a brown colour that absorbs maximally at 460 nm. The combined solutions of buffered O ‐dianisidine and H 2 O 2 (200 µl) were incubated with an aliquot of the tissue homogenate sample (7 µl) in specified wells of a microplate.…”