Protective role of luteolin against bisphenol A-induced renal toxicity through suppressing oxidative stress, inflammation, and upregulating Nrf2/ARE/ HO-1 pathway.

For the development of renal diseases, oxidative stress (OS) is reasoned to be one of the risk factors. For the treatment or prevention of the renal disease, the use of antioxidants could be a hopeful therapeutic mediation as they retard or block the oxidative reaction along with the inflammatory process. Luteolin (Lut) is a plant flavonoid, a pharmacologically active component normally found in glycosylated forms in basic perilla leaf, green pepper, celery, seed, honeysuckle bloom, and chamomile blossom; it exhibits antioxidant activity. In this investigation, we explored the nephroprotective activity of Lut on bisphenol A (BPA)-induced nephron toxicity in rats. Orally administering Lut (100 and 200 mg/kg) diminished BPA-induced anomalies in the kidney, blood urea nitrogen, creatinine, and serum uric acid levels. Lut therapy reduced the BPA-influenced generation of inflammatory mediators, inclusive of tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta. This was coupled with significant improvement in kidney histopathologic features. Lut enhanced the nuclear factor-like 2 (Nrf2) and heme oxygenase 1 (HO-1) expression, which showed protection against OS induced by BPA. The current outcomes of the study showed that Lut has a strong reactive oxygen species scavenging property and potentially decreases the lipid peroxidation as well as inhibits DNA damage in renal toxicity induced by BPA. In conclusion, the potential antioxidant effect of Lut may be because of its modulatory effect on the Nrf2/antioxidant response element (ARE)/HO-1 pathway, which means it protects the kidney from BPA-induced oxidative injury. © 2019 IUBMB Life, 2019.

Role of Aqueous Extract of the Wood Ear Mushroom, Auricularia polytricha (Agaricomycetes), in Avoidance of Haloperidol-lnduced Catalepsy via Oxidative Stress in Rats.

Haloperidol-induced catalepsy is an animal model of a psychotic disorder that may be associated with neurodegeneration and free radical damage. Auricularia polytricha is effective in both prevention and treatment of numerous types of neurological disorders. In the present study, anticataleptic activity of aqueous extract of A polytricha (AEAP) at different doses (400 and 600 mg/kg, respectively, p.o.) was studied using haloperidol-induced (1 mg/ kg, i.p.) catalepsy in rats. Repeated treatment with haloperidol (1 mg/kg, i.p.) on each other day for 15 days (days 5, 10, and 15) significantly induced catalepsy in rats. The effect of AEAP at different doses (400 and 600 mg/kg, p.o.) on levels of superoxide dismutase, catalase, and glutathione reductase as well as inhibition of lipid peroxidation in the forebrain region was assessed. After 15 days of treatment, AEAP (400 and 600 mg/kg) significantly inhibited haloperidol-induced catalepsy. Treatment with AEAP (400 and 600 mg/kg) exhibited significant elevation in the levels of superoxide dismutase, catalase, and glutathione reductase as well as lipid peroxidation in the forebrain region compared to the haloperidol-treated group. The study concludes that AEAP (400 and 600 mg/kg) significantly protects animals against haloperidol-induced catalepsy.

Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity.

The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.

Pharmacological Evaluation of Novel Flavone from Morus alba in Pentylenetetrazole-Induced Kindling and Oxidative Stress.

The present study was designed to explore the effect of chronic administration of a new flavone [morusflavone, 5,7,4'-trihydroxy-8-(γ,γ-dimethylallyl)-2',3'-(10'-hydroxy-9',10'-dimethyl-cyclohex-8-enyl)-flavone (compound 1)] at doses of 25, 50, and 100 mg/kg, orally (p.o.) to pentylenetetrazole-induced kindling in rats (a model of human epilepsy). Compound 1 and four other compounds were isolated from the stem bark of Morus alba. The structure of compound 1 was elucidated and established using standard spectroscopic techniques, and malondialdehyde (MDA) and glutathione (GSH) were estimated as oxidative markers in brain tissues of rodents. The progression of kindling in rats was effectively and significantly suppressed at doses of 25, 50, and 100 mg/kg of compound 1. In addition, increased the levels of MDA and decreased levels of glutathione were also reversed by compound 1 in kindled rats. Compound 1 treatment was able to restore the reduced glutathione level in the brain tissues of PTZ-kindled rats, thus proving its neuroprotective potential.