Zebrafish: An emerging model system to study liver diseases and related drug discovery.

The zebrafish has emerged as a powerful vertebrate model for studying liver-associated disorders. Liver damage is a crucial problem in the process of drug development and zebrafish have proven to be an important tool for the high-throughput screening of drugs for hepatotoxicity. Although the structure of the zebrafish liver differs to that of mammals, the fundamental physiologic processes, genetic mutations and manifestations of pathogenic responses to environmental insults exhibit much similarity. The larval transparency of the zebrafish is a great advantage for real-time imaging in hepatic studies. The zebrafish has a broad spectrum of cytochrome P450 enzymes, which enable the biotransformation of drugs via similar pathways as mammals, including oxidation, reduction and hydrolysis reactions. In the present review, we appraise the various drugs, chemicals and toxins used to study liver toxicity in zebrafish and their similarities to the rodent models for liver-related studies. Interestingly, the zebrafish has also been effectively used to study the pathophysiology of nonalcoholic and alcoholic fatty liver disease. The genetic models of liver disorders and their easy manipulation provide great opportunity in the area of drug development. The zebrafish has proven to be an influential model for the hepatic system due to its invertebrate-like advantages coupled with its vertebrate biology. The present review highlights the pivotal role of zebrafish in bridging the gap between cell-based and mammalian models.

Catechins prevent obesity-induced kidney damage by modulating PPARγ/CD36 pathway and gut-kidney axis in rats.

Obesity is an epidemic and a growing public health concern worldwide. It is one of the significant risk factors for developing chronic kidney disease. In the present study, we evaluated the preventive effect of green tea catechins (GTC) against obesity-induced kidney damage and revealed the underlying molecular mechanism of action. Various green tea catechins were quantified in the catechins-rich fraction using HPLC. In vitro, the palmitic and oleic acid-treated NRK-52E cells showed reduced fat accumulation and modulated expressions of PPARγ, CD36, and TGFß after GTC treatment. In vivo, rats were fed with a high-fat diet (HFD), and the effect of GTC was assessed at 150 and 300 mg/kg body weight doses. HFD-fed rats showed a significant reduction in weight gain and improved serum creatinine, urea, and urine microalbumin levels after GTC treatment. The improved adipokines and insulin levels in GTC treated groups indicated the insulin-sensitizing effect. Histopathology revealed reduced degenerative changes, fibrous tissue deposition, and mesangial matrix proliferation in GTC treated groups. GTC treatment also downregulated the gene expressions of lipogenic and inflammatory factors and improved the altered expressions of CD36 and PPARγ in the kidney tissue. Further, GTC prevented gut dysbiosis in rats by promoting healthy microbes like Akkermansia muciniphila and Lactobacillus reuteri. Faecal metabolome revealed reduced saturated fatty acids, and improved amino acid levels in the GTC treated groups, which help to maintain gut health and metabolism. Overall, GTC prevented obesity-induced kidney damage by modulating PPARγ/CD36 signaling and maintaining gut health in rats.

Peroxisome proliferator-activated receptor gamma as a therapeutic target for hepatocellular carcinoma: Experimental and clinical scenarios.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Viral hepatitis is a significant risk factor for HCC, although metabolic syndrome and diabetes are more frequently associated with the HCC. With increasing prevalence, there is expected to be > 1 million cases annually by 2025. Therefore, there is an urgent need to establish potential therapeutic targets to cure this disease. Peroxisome-proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that plays a crucial role in the patho-physiology of HCC. Many synthetic agonists of PPARγ suppress HCC in experimental studies and clinical trials. These synthetic agonists have shown promising results by inducing cell cycle arrest and apoptosis in HCC cells and preventing the invasion and metastasis of HCC. However, some synthetic agonists also pose severe side effects in addition to their therapeutic efficacy. Thus natural PPARγ agonists can be an alternative to exploit this potential target for HCC treatment. In this review, the regulatory role of PPARγ in the pathogenesis of HCC is elucidated. Furthermore, the experimental and clinical scenario of both synthetic and natural PPARγ agonists against HCC is discussed. Most of the available literature advocates PPARγ as a potential therapeutic target for the treatment of HCC.

Copigmentation and UPLC-ESI-MS/MS of anthocyanin in Ipomoea nil as potential source of food colorant.

Anthocyanins are good alternative to synthetic dyes for food, pharmaceutical and nutraceutical industries. Owing to their wide occurrence in plant kingdom, an UPLC-ESI-MS/MS method was used to identify and quantify the constituents in flowers of Ipomoea nil. The qualitative evaluation of I. nil results in the characterisation of acylated and non-acylated anthocyanins. Besides characterisation, the total phenolic contents in different fractions of I. nil were found to be 49.69 ± 1.74 and 331.54 ± 1.14 mg GAE/g, respectively. The total anthocyanins content was also determined by spectrophotometer and found to be 5.89 mg/100g of cyanidin-3-O-glucoside equivalent. The antioxidant activity of different fraction of I. nil was evaluated by different assays (DPPH●, ABTS●+ and FRAP). In the direction of natural colour stability, we had studied different stabilising agents/copigments and were found to provide stability up to 140 °C. The extracted anthocyanins were evaluated for acute oral toxicity studies and observed to be non-toxic and may direct the use of I. nil for human consumption.

Health-Related Quality of Life Among Liver Disorder Patients in Northern India.

Objective: The present study aims to determine the health-related quality of life (HRQoL) among liver disorder patients being treated in tertiary care hospital in north India and exploration of factors affecting HRQoL. Methodology: The HRQoL was assessed among 230 patients visiting either the outpatient department (OPD) or those admitted in high dependency unit (HDU) or liver intensive care unit (ICU) using direct measuring tools such as Euro QoL five-dimension questionnaire (EQ-5D) and EQ visual analog scale. Multivariate regression was used to explore the factors influencing HRQoL. Results: Mean EQ-5D scores among chronic hepatitis and compensated cirrhosis patients were 0.639 ± 0.062 and 0.562 ± 0.048, respectively. Among those who were admitted in the ICU or HDU, mean EQ-5D score was 0.295 ± 0.031. At discharge, this score improved significantly to 0.445 ± 0.055 (P < 0.001). The multivariate results implied that HRQoL was significantly better among patients with lower literacy level (P = 0.018) and those treated in OPD settings (P < 0.001). Conclusion: HRQoL is impaired among patients suffering from liver disorders specifically those admitted in ICU. Further, there is a need to generate more evidence to explore the impact of determinants and treatment-associated costs on the HRQoL.

Tinospora cordifolia activates PPARγ pathway and mitigates glomerular and tubular cell injury in diabetic kidney disease.

BACKGROUND: Diabetic Kidney Disease (DKD) is a common complication of diabetes and a leading cause of end-stage renal disease progression. Therefore, therapeutic strategies are desirable to mitigate the progression of disease into more severe consequences. Hypothesis/Purpose:Tinospora cordifolia is a traditionally known antidiabetic plant; however, its effect against DKD remains unexplored. Therefore, in the present study, we assessed the efficacy and mechanism of action of Tinospora cordifolia extract (TC) against DKD. METHODS: The molecular interaction of the various phytoconstituents of TC with PPARγ were analyzed in silico. The effect of TC was studied on the viability, cell cycle, and gene expressions (PPARγ, TGFß, and αSMA) in high glucose treated NRK-52E and SV40 MES13 cells. Further, streptozotocin-induced diabetic rats were treated with TC for eight weeks, and the effects on different biochemical, histological and molecular parameters were studied. RESULTS: In silico analysis revealed the integration of various phytoconstituents of TC with PPARγ. It further increased PPARγ and decreased TGFß and αSMA expressions in NRK-52E and SV40 MES13 cells. In diabetic rats, TC improved the fasting blood glucose, serum urea, and creatinine levels. It also lowered the urine microalbumin and advanced glycation end products (AGEs) levels. Histopathological studies revealed the preventive effect of TC on degenerative changes, mesangial proliferation and glomerular hypertrophy. Further, it reduced the inflammation and fibrotic changes in the kidney tissue estimated by various markers. The kidney tissue and gene expression analysis revealed the augmented levels of PPARγ after TC treatment. CONCLUSION: In conclusion, TC exerted the protective effect against DKD by inhibiting inflammation and fibrogenesis through the activation of PPARγ dependent pathways.

Out-of-pocket expenditure and catastrophic health expenditure for hospitalization due to injuries in public sector hospitals in North India.

BACKGROUND: Injuries are a major public health problem, resulting in high health care demand and economic burden. They result in loss of disability adjusted life years (DALYs) and high out-of-pocket expenditure. However, there is little evidence on the economic burden of injuries in India. We undertook this study to report out-of-pocket expenditure and the prevalence of catastrophic health expenditure for injuries related hospitalizations in public sector hospitals in North India. Further, we also evaluate the determinants of catastrophic health expenditure. METHODS AND ANALYSIS: A prospective observational study was conducted. Participants were recruited from three hospitals for all injury cases. Data were collected via face-to-face baseline interviews and follow-up interviews over the phone at 1, 2, 4 and 12 months post-injury. Prevalence of catastrophic health expenditure (more than 30% of consumption expenditure) and impoverishment (International dollar 1.90) were estimated. RESULTS: Road traffic injuries (57%) were the leading cause of injury. Direct out-of-pocket expenditure for hospitalizations was INR 16,768 (USD 263) while indirect productivity loss was INR 8,164 (USD 128). The prevalence of catastrophic expenditure was 22.2% with 12.2% slipping below poverty line. Prevalence of catastrophic health expenditure and impoverishment was higher and significantly associated with poorest quintile, tertiary care hospital and increased duration of hospitalization (p< 0.001). CONCLUSION: The economic impact of injuries is notably high both in terms of out-of-pocket expenditure and productivity loss. A high proportion of households experienced catastrophic expenditure and impoverishment following an injury, highlighting need for programs to prevent injuries.