Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO-1/NLRP3 and TGF-ß expression.

Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-α, and IL-6) and fibrosis-related genes (TGF-ß and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN.

The Role of TLR4, TNF-α and IL-1ß in Type 2 Diabetes Mellitus Development within a North Indian Population.

This study investigated the role of IL-1ß-511 (rs16944), TLR4-896 (rs4986790) and TNF-α-308 (rs1800629) polymorphisms in type 2 diabetes mellitus (T2DM) among an endogamous Northern Indian population. Four hundred fourteen participants (204 T2DM patients and 210 nondiabetic controls) were genotyped for IL-1ß-511, TLR4-896 and TNF-α-308 loci. The C allele of IL-1ß-511 was shown to increase T2DM susceptibility by 75% (OR: 1.75 [CI 1.32-2.33]). Having two parents affected by T2DM increased susceptibility by 5.7 times (OR: 5.693 [CI 1.431-22.648]). In this study, we have demonstrated a conclusive association with IL-1ß-511 locus and IL-1ß-511-TLR4-896 diplotype (CC-AA) and T2DM, which warrants further comprehensive analyses in larger cohorts.

Genetic variation of MHC Class I polymorphic Alu insertions (POALINs) in three sub-populations of the East Midlands, UK.

BACKGROUND: Alu elements are highly researched due to their useful nature as markers in the study of human population genetics. Recently discovered Major Histocompatibility Complex (MHC) polymorphic Alu insertions (POALINs) have not been examined extensively for genetic variation and their HLA associations. AIMS: The aim of this study is to assess the genetic variation between three populations using five recently discovered POALINs. METHODS AND SUBJECTS: The study examined 190 healthy, unrelated subjects from three different populations in the East Midlands (UK) for the presence or absence of five Alu elements (AluHG, AluMICB, AluHJ, AluTF and AluHF) via the polymerase chain reaction followed by gel electrophoresis. Data were analysed for genetic variation and phylogenetic analyses. RESULTS: All Alus were polymorphic in study populations. Appreciable allele frequency variation was observed at a number of loci. The British population was significantly different from both the Punjabi Jat Sikh and Gujarati Patel populations, although showing a closer genetic relationship to the Punjabi Jat Sikh population than the Gujarati Patel population (Nei's DA = 0.0031 and 0.0064, respectively). CONCLUSIONS: MHC POALINs are useful markers in the investigation of genetic variation and the assessment of population relationships, and may have some bearing on disease associations due to their linkage disequilibrium with HLA loci; this warrants further studies.