Arsenic Induces Continuous Inflammation and Regulates Th1/Th2/Th17/Treg Balance in Liver and Kidney In Vivo

Abstract

Numerous studies on arsenic-induced hepatonephric toxicity including cancer have been reported. Given that chronic inflammatory response and immune imbalance are associated with oncogenesis, we investigated whether arsenic could influence the hepatic and nephritic expression of inflammatory factors and the differentiation of T cells. Mice were exposed to NaAsO2 (0, 25, and 50 mg/L) for 1 and 3 months. Our data showed the destruction of the structure and inflammatory infiltration in the liver. The arsenic markedly increased the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The myeloperoxidase (MPO) activities increased in the liver at 25 and 50 mg/L arsenic for 3 months as well as in the kidney at both 1 and 3 months. An increased expression of inflammatory indicators (IL-1β, IL-12, and TNF-α) at 25 and 50 mg/L arsenic for 1 and 3 months in the liver and kidney, as well as IL-1β in the liver for 3 months and in the kidney at 50 mg/L for 1 and 3 months were demonstrated in our experiments. Besides, a definite tendency toward Th1/Th17 cytokines in the liver while Th2/Th17 cytokines in kidney was also observed by arsenic. Moreover, arsenic enhanced the expression of MAPK/Nrf2/NF-κB signaling molecules. In conclusion, the results of the study suggested that arsenic induces continuous immune-inflammatory responses in the liver and kidney.

Arsenic exposure induced renal fibrosis via regulation of mitochondrial dynamics and the NLRP3‐TGF‐β1/SMAD signaling pathway

“…Our data was in keeping with other studies, for instance, it was reported that arsenic caused renal histopathological changes of inflammatory cell infiltration, renal TECs desquamated, oozing blood, and glomerular atrophy. 16,43 NaAsO 2 -induced fibrosis in the kidney was also supported by previous studies where similar findings had been reported. 44,45 The adverse outcome pathway that how NaAsO 2 triggered kidney damage remains to be determined.…”

“…15 In experimental animals, arsenic exposure can cause renal injury and interstitial fibrosis, including the pathology of mitochondria. 3,16,17 And the nephrotoxicity of arsenic was also confirmed by in vitro experiments. 14,18 Understanding the mechanism of arsenic exposure-induced renal fibrosis can help to the prevention and control of arsenic poisoning.…”

Profiling of Peripheral TRBV and CD4+CD25+ Treg in CHB Patients with HBeAg SC during TDF Treatment

“…In the course of antiviral treatment, CD4+CD25+ Treg frequency was declining in peripheral blood of CHB, and the decreasing degree of Tregs was greater in the HBeAg SC compared with that in the non-SC group, and the Treg frequency was higher in CHB subjects with active HBV replication [ 2 , 34 ]. Furthermore, the Treg frequency is positively correlated with serum ALT level [ 30 , 35 ], which was reconfirmed in our current study. The ALT levels usually reflect self-renewal metabolism of hepatocyte, and elevated serum ALT levels suggest the presence of active inflammation and the degree of hepatocyte injury caused by immune response against HBV [ 36 , 37 ].…”

Molecular Mechanisms of Cellular Injury and Role of Toxic Heavy Metals in Chronic Kidney Disease

“…Recent studies in mice showed that exposure to As activates the MAPK/NF-κB and NRF2 pathways in kidney. While activation of these pathways may improve cell survival, exposure to As also led to increased activity of myeloperoxidase and increased expression of inflammatory cytokines, such as IL-1α, IL-6, IL-12, and TNF-α, which may lead to an inflammatory response [ 118 , 119 ]. Furthermore, elevated expression of inflammatory cytokines was shown to disrupt homeostasis of helper T cell populations (Th1/Th2/Th17/Treg).…”

“…The balance among T cells populations is critical to maintain proper immune function. Exposure to As alters the balance and leads to inflammation and immunosuppression [ 118 , 120 ]. Use of newer immunotherapeutics and their impact on kidney function is a new and expanding area of research.…”