Occupational Paraquat and Glyphosate Exposure May Decline Renal Functions among Rural Farming Communities in Sri Lanka.

Extensive use of herbicides is common among rural agricultural workers in Sri Lanka. Recent studies have postulated their role in the development of chronic kidney disease of unknown etiology (CKDu). Paraquat and glyphosate are leading herbicides used by sugarcane farmers (SF), hence occupational exposure is inevitable. This study examined the expression of urinary paraquat, glyphosate and biomarkers among residential SF in CKDu emerging regions, Warunagama (WA) and Rahathangama (RH), in the Uva Province with non-endemic Matara (MA) in the Southern Province of Sri Lanka. Urinary glyphosate, Paraquat, kidney injury molecule -1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and ß2-microglobulin (B2M) were determined using enzyme-linked immunosorbent assays (ELISA). Urinary creatinine, microalbumin, serum creatinine (SCr), serum cystatin C, estimated glomerular filtration rate (eGFR), and albumin creatinine ratio (ACR) were also assessed. Generally, herbicide residues and kidney injury biomarkers were higher in SF compared to the non-endemic MA. Creatinine-adjusted urinary glyphosate and paraquat levels were significantly higher in WA compared to MA. ACR in RH (median 14.9; IQR 5.4-393.1 mg/g) and WA (23.7; 11.5-64.6) was significantly higher than MA (4.3; 2.2-6.7). This study reports 39 individuals with impaired kidney function among SF in Sri Lanka for the first time. Urinary NGAL levels were significantly higher in both WA (median 2.14; IQR 1.28-6.15 ng/mg Cr) and RH (3.09; 1.15-9.09) compared to MA (1.28; 0.56-2.81). However, urinary KIM-1 levels in RH (3.2; 1.29-106.1 ng/g Cr) and WA (3.6; 1.94-115.1) were not significantly higher in MA (1.74; 0.76-116.9). Urinary NGAL (r = 0.493), eGFR (r = -0.147) and ACR (r = 0.171) significantly correlated with urinary glyphosate, but not with urinary paraquat levels. Urinary KIM-1 levels did not correlate with either urinary glyphosate or paraquat, while urinary B2M and serum cystatin C levels showed significant correlation with urinary glyphosate levels. The current study reports higher urinary herbicide levels among sugarcane farmers in WA and RH, and that is potentially linked to the subsequent decline in kidney function, as indicated by ACR, eGFR, and NGAL. We posit that these indicators may serve as markers to detect renal injury among herbicide-exposed SF in Rural Sri Lanka.

Isosteviol sodium protects heart embryonic H9c2 cells against oxidative stress by activating Akt/GSK-3ß signaling pathway.

Oxidative stress plays a crucial role in pathogenesis of various cardiovascular diseases. Recent studies reported that isosteviol sodium (STVNa) harbor cardioprotective properties. Here, we explore the potential cardioprotective effect of STVNa on H2 O2 -induced oxidative stress on heart embryonic H9c2 cardiomyocytes and the underlying mechanism. We have found that STVNa pretreatment improved cell viability, nuclear morphology and prevented LDH release induced by oxidative stress. STVNa pretreatment also reduced production of reactive oxygen species, preserved mitochondrial function, restored biological antioxidant defense systems and prevented cell death. Western blotting analysis revealed that STVNa regulated the mitochondrial related pro- and anti-apoptotic protein (Bax and Bcl-2 respectively) levels, increased phosphorylation of Akt (ser473) and GSK-3ß (ser9) and promoted binding between HK-II and mitochondria under the normal or oxidative stress conditions. LY294002, a PI3K inhibitor, abolished cytoprotective effects of STVNa by inhibiting activation of Akt and GSK-3ß. Based on these findings, we conclude that STVNa protects H9c2 cells against oxidative stress by activating Akt/GSK-3ß signaling pathway, which, in turn, leads to recruitment of HK-II to mitochondria and regulating Bcl2/Bax levels.