NA. Laryngoscope, 128:2029-2033, 2018.

No abstract

Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B).The immortalised human bronchial epithelial cell line (BEAS-2B) was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL)-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays.Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B.Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

Hyperuricemia is an abnormal metabolic condition characterized by an increase in uric acid levels in the blood. It is the cause of gout, manifested by inflammatory arthritis, pain and disability. This study examined the possible ameliorative impacts of parsley (PAR) and celery (CEL) as hypouricemic agents at biochemical, molecular and cellular levels. PAR and CEL alone or in combination were orally administered to hyperuricemic (HU) mice and control mice for 10 consecutive days. Serum levels of uric acid and blood urea nitrogen (BUN), xanthine oxidase activity, antioxidants, inflammatory (IL-1β and TNF-α) and anti-inflammatory cytokines (IL-10) were measured. mRNA expression of urate transporters and uric acid excretion genes in renal tissues were examined using qRT-PCR (quantitative real time PCR). Normal histology and immunoreactivity of transforming growth factor-beta 1 (TGF-β1) in kidneys was examined. Administration of PAR and CEL significantly reduced serum BUN and uric acids in HU mice, ameliorated changes in malondialdehyde, catalase, and reduced glutathione, glutathione peroxidase (GPX), IL-1β, TNF-α and IL-10 in hyperuricemic mice. Both effectively normalized the alterations in mURAT-1, mGLUT-9, mOAT-1 and mOAT-3 expression, as well as changes in TGF-β1 immunoreactivity. Interestingly, combined administration of PAR and CEL mitigated all examined measurements synergistically, and improved renal dysfunction in the hyperuricemic mice. The study concluded that PAR and CEL can potentially reduce damaging cellular, molecular and biochemical effects of hyperuricemia both individually and in combination. Hyperuricemia (HU) is defined as an increase in the levels of uric acid over normal ranges (6 mg/dL in females and 7 mg/dL in males) 1,2. HU is associated with meat and seafood ingestion, hypertension and obesity 2-4. Advanced HU is associated with gout 5. Gout results in deposition of urate in soft tissues and joints, and arthritis in men over 40 years old 5. Uric acid (UA) is the end product of the catabolism of purine compounds in the liver. UA is excreted mainly by the kidneys and to a lesser extent by the gastrointestinal tract 6,7. It is degraded by gut microbiota (one third) in a process known as intestinal uricolysis 8. The remaining two thirds depends on interchange between UA secretion and reabsorption in the kidney tubules 8-10. Treatment of gout mainly depends on allopurinol (ALP). ALP is an inhibitor of xanthine oxidase and stimulates renal excretion of UA 10,11. Other anti-inflammatory drugs (indomethacin) can be used, but these may cause side effects 11. Therefore, identifying safe herbal medications is the goal for both patients and physicians. The use of organic drugs and therapies is cost-effective 12. The positive and promising effects of medicinal herbs on renal diseases, infertility, liver disorders and diabetes are clearly established and are accepted by patients and clinicians as a safe medication for these disorders 13-17 .

This is the first demonstration that bile acids induce TGF-β1 and MMP-9 in pharyngeal cells. TGF-β1 is considered a master switch for EMT, while MMP-9 is a part of the EMT proteome which degrades basement membranes. This implies a potential role for bile acids in pharyngeal carcinogenesis through the mechanism of EMT and suggests potential novel therapeutic targets.

In agriculture, gibberellic acid (GA3) is commonly used with extreme dangers for public health. The current research evaluates the improving effects of n‐acetyl cysteine (NAC, 150 mg/kg bw) co‐administered with GA3 (55 mg/kg bw) mediated testicular injury. Twenty‐four male albino rats were split into 4 groups: Negative control (CNT), NAC group, positive GA3 group and protective group, co‐administered NAC plus GA3. On day 21, rats were anesthetised then euthanised by decapitation. Blood samples were collected; testicular samples were taken for semen analysis, serum chemistry, RNA extraction, histological and antioxidants markers examination. Our results revealed a significant decline p < .05 of catalase level and total antioxidant capacity. There was a substantial rise of MDA concentration in GA3‐treated rats along with a considerable decrease of the antioxidant markers (SOD, GSH) and serum male reproductive hormones. In GA3‐treated rats, an overexpression of the inflammatory cytokines (TNF‐α, IL‐1β) and anti‐inflammatory cytokine IL‐10 with boost mRNA expression of nuclear factor‐kappa (NFkB) were confirmed. There was downregulation of steroidogenesis genes and decrease in sperm quality and concentration with an increase in sperm abnormalities, all were reported in GA3‐treated rats. NAC treatment significantly increased the antioxidant state, testicular function beside structural germ cell and seminiferous tubules histology accompanied by upsurge of steroidogenic mRNA expressions (P450scc and 3β‐HSD) and downregulated the pro‐inflammatory cytokines mRNA expression (TNF‐α, IL‐1β). These results confirm the antioxidant capability of NAC and afford robust evidence about the ameliorative effect of the NAC to attenuate the testicular injury induced by GA3 through modulation of the antioxidant defence system, steroidogenic and pro‐inflammatory cytokines mRNA expression.

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.

Nonalcoholic fatty liver disease (NAFLD) has become one of the public health problems globally. The occurrence of NAFLD is usually accompanied by a series of chronic metabolic diseases, with a prevalence rate is 25.24% among adults worldwide. Therefore, NAFLD seriously affects the quality of life in patients and causes a large economic burden. It has been reported that puerarin has the function of lowering the serum lipids, but due to the complexity of NAFLD, the specific mechanism of action has not been clarified. The aim of this study was to evaluate the preventive or ameliorating effects of two doses of puerarin (0.11% and 0.22% in diet) on high-fat and high-fructose diet (HFFD)-induced NAFLD in rats. The rats were fed with HFFD-mixed puerarin for 20 weeks. The results showed that puerarin ameliorated the levels of lipids in the serum and liver. Further exploration of the mechanism found that puerarin ameliorated hepatic lipid accumulation in NAFLD rats by reducing the expression of Srebf1, Chrebp, Acaca, Scd1, Fasn, Acacb, Cd36, Fatp5, Degs1, Plin2, and Apob100 and upregulating the expression of Mttp, Cpt1a, and Pnpla2. At the same time, after administration of puerarin, the levels of antioxidant markers (superoxide dismutase, glutathione peroxidase, and catalase) were significantly increased in the serum and liver, and the contents of serum and hepatic inflammatory factors (interleukin-18, interleukins-1β, and tumor necrosis factor α) were clearly decreased. In addition, puerarin could ameliorate the liver function. Overall, puerarin ameliorated HFFD-induced NAFLD by modulating liver lipid accumulation, liver function, oxidative stress, and inflammation.