Arsenic (As) contamination of the rice agro-ecosystem is a major concern for rice farmers of South East Asia as it imposes a serious threat to human and animal life; thus, there is an unrelenting need to explore the ways by which arsenic stress mitigation could be achieved. In the present investigation, we explore the effect of zinc (Zn²⁺) supplementation using the seed priming technique for the mitigation of As-induced stress responses in developing rice seedlings. In addition to the physiological and biochemical attributes, we also studied the interactive effect of Zn²⁺ in regulating As-induced changes by targeting antioxidant enzymes using a computational approach. Our findings suggest that Zn²⁺ and As can effectively modulate redox homeostasis by limiting ROS production and thereby confer protection against oxidative stress. The results also show that As had a significant impact on seedling growth, which was restored by Zn²⁺ and also minimized the As uptake. A remarkable outcome of the present investigation is that the varietal difference was significant in determining the efficacy of the Zn²⁺ priming. Further, based on the findings of computational studies, we observed differences in the surface overlap of the antioxidant target enzymes of rice, indicating that the Zn²⁺ might have foiled the interaction of As with the enzymes. This is undoubtedly a fascinating approach that interprets the mode of action of the antioxidative enzymes under the metal/metalloid-tempted stress condition in rice by pointing at designated targets. The results of the current investigation are rationally significant and may be the pioneering beginning of an exciting and useful method of integrating physiological and biochemical analysis together with a computational modelling approach for evaluating the stress modulating effects of Zn²⁺ seed priming on As-induced responses in developing rice seedlings.

Objective: Gastroesophageal reflux is thought to be a risk factor for laryngotracheal stenosis. Bile acids are a component of gastric refluxate and have previously been implicated in the development of fibrosis in other airway subsites. There is clear evidence that bile acids reflux into the upper airway. We therefore investigated the potential role of bile acids in the pathophysiology of laryngotracheal fibrosis and stenosis, specifically investigating the highly conserved process of epithelial–mesenchymal transition (EMT).Study Design: Translational research study.Methods: Human primary tracheal epithelial cells (PTECs) were challenged with the four most common digestive bile acids (cholic, chenodeoxycholic, deoxycholic, and lithocholic). EMT markers transforming growth factor (TGF)‐β1, Matrix metalloproteinase (MMP)‐9, and procollagen proteins were measured in the supernatant at 48 hours via enzyme‐linked immunosorbent assay. Real‐time polymerase chain reaction was also used to measure E‐cadherin and fibronectin expression.Results: Significantly greater concentrations of TGF‐β1 and MMP‐9 were measured in the culture supernatants of cells treated with each bile acid at 10 µmol/L. Lithocholic acid and deoxycholic acid induced significantly increased expression of procollagen protein. Upregulation of fibronectin and downregulation of E‐cadherin were observed with all bile acids, except for deoxycholic acid.Conclusion: This is the first proof of principle demonstration that physiologically relevant bile acid challenge induces EMT mechanisms in PTECs. This implies a potential role for bile acids in laryngotracheal scarring and airway remodeling of potential translational significance in laryngotracheal stenosis.Level of Evidence: NA. Laryngoscope, 128:2029–2033, 2018

Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50 mg/kg/BW orally daily for 4 weeks; the GA3 group received 55 mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-administration of chrysin significantly protected the hepatorenal tissue against the deleterious effects of GA3. Chrysin restored the hepatorenal functions and their antioxidant ability to normal levels. Moreover, chrysin modulated the hepatorenal toxic effects of GA3 at the molecular level via the upregulation of the antiapoptotic genes, interleukin-10 (IL-10), hemoxygenase-1, and nuclear factor erythroid 2-related factor 2 expressions; the downregulation of the kidney injury molecule-1 and caspase-3 mRNA expressions; and a decrease in IL-1β and tumor necrosis factor-α secretions. Additionally, the pre-administration of chrysin effectively attenuated the GA3-induced hepatorenal histopathological changes by regulating the immunoexpression of cytochrome P450 2E1 (CYP2E1) and pregnane X receptor, resulting in normal values at the cellular level. In conclusion, chrysin attenuated GA3-induced oxidative hepatorenal injury by inhibiting free-radical production and cytokine expression as well as by modulating the antioxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.

Gentamicin is an effective antibiotic that has been used worldwide for many years. While considered an essential medicine by the WHO, gentamicin can also lead to severe kidney damage. This study explored the ameliorative effects of Glycyrrhiza glabra root extract on gentamicin‐induced renal injury in mice. Four groups of n = 7 mice were used: (a) control; (b) G. glabra‐only; (c) gentamicin‐only; and (d) gentamicin plus G. glabra. Kidney samples were tested for: antioxidant enzyme activity (superoxide dismutase [SOD] and glutathione peroxidase [Gpx]); expression of HO‐1 and nuclear factor erythroid 2‐related factor 2 genes; expression of Cox‐2 and Bax; cytokine levels (IL‐1β, and IL‐6); histopathological anomalies; and standard renal functional component levels (creatinine, urea, and blood urea nitrogen). The effects of gentamicin were generally reversed or normalized following treatment with G. glabra root extract. Gentamicin decreased Gpx and SOD parameters and increased IL‐1 β and IL‐6 levels, but these returned to normal in the G. glabra‐treated group. Gentamicin upregulated tissue levels of Cox‐2 and Bax, and downregulated HO‐1 and Nrf‐2 expression but again, and these levels returned to normal in the group treated with G. glabra. Mice that had received gentamicin exhibited acute renal blood vessel congestion, focal interstitial round cell aggregation, and hydropic degeneration of renal tubular epithelium. However, those that had also received G. glabra showed a normal histopathology. Findings from this study indicate that in mouse models, gentamicin‐induced kidney damage can be reversed or ameliorated by administering G. glabra, so it can be considered as an effective complimentary therapy.

This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and quercetin + AgNPs. After 30 days, blood and brain tissue samples were collected for further studies. AgNP exposure increased lipid peroxidation and decreased glutathione peroxidase, catalase, and superoxide dismutase activities in brain tissue. AgNPs decreased serum acetylcholine esterase activity and γ-aminobutyric acid concentrations. AgNPs upregulated tumor necrosis factor-α, interleukin-1β, and Bax transcript levels. AgNPs reduced the transcripts of claudin-5, brain-derived neurotrophic factor, paraoxonase, nuclear factor-erythroid factor 2 (Nrf2), and Bcl-2. Histopathologically, AgNPs caused various degenerative changes and neuronal necrosis associated with glial cell reactions. AgNPs increased the immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the cerebrum and cerebellum. Oral treatment with quercetin efficiently counteracted the opposing effects of AgNPs on brain tissue via modulation of tight junction proteins, Nrf2, and paraoxonase, and its positive mechanism in modulating pro-inflammatory cytokines and the downregulation of GFAP expression, and the apoptotic pathway. AgNPs also altered the severity of histopathological lesions and modulated GFAP immunostaining in the examined tissue.