Obesity is implicated as a significant risk factor for chronic kidney disease (CKD). High plasma free fatty acid levels observed with obesity impairs the endoplasmic reticulum (ER) and cause ER stress. Chemical chaperones, which relieve ER stress, such as 4‐phenylbutyrate (4‐PBA) have been shown to protect the liver and pancreas against obesity‐induced organ damage; however, their protective role in obesity‐induced renal damage is unknown. Thus, we investigated the nephroprotective role of 4‐PBA in an in vitro model of palmitic acid (PA)‐induced ER stress and renal injury using normal rat kidney cells (NRK‐52E). Cells were divided into four groups: Control, 250 μM PA‐treated, 5 mM 4‐PBA‐treated, and 4‐PBA+PA co‐treated. After 24 h of PA and/or 4‐PBA treatments, cell viability and caspase‐3/7 activity (a marker of apoptosis) were determined. Immunoblot analyses were performed to quantitate the levels of ER stress markers ‐ glucose‐regulated protein (GRP78) and C/EBP homologous protein (CHOP) ‐ in renal cells. Exposure to PA significantly reduced the viability (81.3% to that of control) in NRK‐52E cells, and markedly increased the activity of caspase‐3/7 activity (2‐fold increase over control) and the expression of ER stress markers GRP78 and CHOP (1.6 and 2 folds over control respectively) at P‐value < 0.05. Intriguingly, cells treated with 4‐PBA were protected from PA‐induced ER stress and apoptotic cell death. Our studies demonstrate that 4‐PBA acts as nephroprotectant and prevents fatty acid‐induced ER stress and apoptosis in renal cells. Further investigations in vivo are required to validate the therapeutic potential of 4‐PBA to protect the kidney and prevent the development of CKD during obesity.
Grant Funding Source: Supported by Qatar Univ. Student Research Grants # QUST‐CPH‐FALL‐12/13‐6 and QUST‐CPH‐SPR‐12/13‐3.
Background: Worldwide, the prevalence of hepatitis B virus (HBV) infection is decreasing particularly in the vaccinated population. However, there are foci of increased transmission particularly in localized communities and within families. Objective: This study aimed at identifying HBV infection status among family members (FMs) of a cohort of HBsAg positive index cases (ICs) living in a village near Ismailia City, North-East Egypt. Design and participants: The study targeted ICs with chronic hepatitis B and their FMs. All were inquired for sociodemographic data, previous vaccination, kinship, and risk factors. All were tested for hepatitis markers and in HBcAb positive sera, HBV DNA and ALT were added. Results: The study included 96 participants including 14 ICs, 51 (53.1%) were females and 73 (76%) self-reported receiving hepatitis B vaccine after birth. Among 82 FMs, HBcAb was found in 49 (59.76%) of whom overt and occult HBV were diagnosed in 24 (49%) and 18 (36.7%). HBs Ag and HBcAb were more frequent in unvaccinated compared to vaccinated FMs; being 60.9% vs. 32.9% for HBsAg (p=0.017) and 91.3% vs. 57.5% for HBcAb (p=0.003). Among the FMs, active HBV were more related to male than female ICs (54.9% vs. 45.2%, p=0.73) while among children, it is more related to females more than male ICs (38.9% vs. 25%, p=0.33). In all HBsAg positive participants, HBeAg was negative and HBV DNA load was higher among female than male ICs (median 3500 vs. 2594.5 IU/mL, p=0.82). Conclusion: The study shows a high rate of HBV transmission among FMs of HBsAg carriers living in a remote area in North-East Egypt. Both overt and occult HBV infections were frequent despite previous vaccination.
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