Protective role of HO‐1 against acute kidney injury caused by cutaneous exposure to arsenicals

Srivastavá, R. C.; Muzaffar, Suhail; Khan, Jasim; Traylor, Amie M.; Żmijewski, Jaroslaw W.; Curtis, Lisa M.; George, James F.; Ahmad, Aftab; Antony, Veena B.; Agarwal, Anupam; Athar, Mohammad

doi:10.1111/nyas.14475

Cited by 10 publications

(6 citation statements)

References 64 publications

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“…Similarly, acute kidney injury associated with tubular cell apoptosis, increase in the levels of serum creatinine, and the upregulation of the kidney injury markers KIM-1 and NGAL has been observed in mice treated topically with lewisite (Srivastava et al, 2018 ). Similar to the results in the skin, lewisite induces ER stress in kidneys, as indicated by the upregulation of ATF4 and CHOP (Srivastava et al, 2020 ). Eyes are also highly sensitive to lewisite exposure, and lewisite-induced ocular injury is characterized by edema and blepharospasm (abnormal eyelid muscle contraction).…”

Section: Arsenicals As Chemical Warfare Agentssupporting

confidence: 77%

Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

et al. 2022

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Worldwide, more than 200 million people are estimated to be exposed to unsafe levels of arsenic. Chronic exposure to unsafe levels of groundwater arsenic is responsible for multiple human disorders, including dermal, cardiovascular, neurological, pulmonary, renal, and metabolic conditions. Consumption of rice and seafood (where high levels of arsenic are accumulated) is also responsible for human exposure to arsenic. The toxicity of arsenic compounds varies greatly and may depend on their chemical form, solubility, and concentration. Surprisingly, synthetic organoarsenicals are extremely toxic molecules which created interest in their development as chemical warfare agents (CWAs) during World War I (WWI). Among these CWAs, adamsite, Clark I, Clark II, and lewisite are of critical importance, as stockpiles of these agents still exist worldwide. In addition, unused WWII weaponized arsenicals discarded in water bodies or buried in many parts of the world continue to pose a serious threat to the environment and human health. Metabolic inhibition, oxidative stress, genotoxicity, and epigenetic alterations including micro-RNA-dependent regulation are some of the underlying mechanisms of arsenic toxicity. Mechanistic understanding of the toxicity of organoarsenicals is also critical for the development of effective therapeutic interventions. This review provides comprehensive details and a critical assessment of recently published data on various chemical forms of arsenic, their exposure, and implications on human and environmental health. Graphical abstract

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Section: Arsenicals As Chemical Warfare Agentssupporting

confidence: 77%

Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

et al. 2022

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“…A major pathway for the toxicities of individual heavy metals is the generation of ROS (20). Itai-itai is a well-characterized example of oxidant-induced tubulopathy (similar to Mesoamerican nephropathy) in individuals with chronic exposure to cadmium in Asian agricultural communities (45,46), and a recent report demonstrates tubulointerstitial nephritis in experimental animals exposed to arsenic compounds (47).…”

Section: Discussionmentioning

confidence: 99%

Potential Mechanisms Involved in Chronic Kidney Disease of Unclear Etiology

Holliday

Bustamante

et al. 2022

CJASN

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Background and objectivesThe etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for Mesoamerican nephropathy in an immigrant dialysis population.Design, setting, participants, & measurementsMigrants with Mesoamerican nephropathy kidney failure (n=52) were identified by exclusion of known causes of kidney disease and compared using a cross-sectional survey with demographically similar patients with kidney failure from other causes (n=63) and age/sex/place of origin–matched healthy participants (n=16). Survey results were extended to the bench; C57BL/6 mice (n=73) received 10–15 weekly intraperitoneal injections of paraquat (a reactive oxygen species–generating herbicide) or vehicle. Kidney function, histology, and expression of organic cation transporter-2 (proximal tubule entry for paraquat) and multidrug and toxin extrusion 1 (extrusion pathway) were examined. Kidney biopsies from Nicaraguan patients with acute Mesoamerican nephropathy were stained for the above transporters and compared with patients with tubulointerstitial nephritis and without Mesoamerican nephropathy.ResultsPatients with Mesoamerican nephropathy and kidney failure were young agricultural workers, almost exclusively men; the majority were from Mexico and El Salvador; and they had prior exposures to agrochemicals, including paraquat (27%). After adjustment for age/sex, exposure to any agrochemical or paraquat was associated with Mesoamerican nephropathy kidney failure (odds ratio, 4.86; 95% confidence interval, 1.82 to 12.96; P=0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; P=0.02, respectively). Adjusted for age/sex and other covariates, 1 year of agrochemical exposure was associated with Mesoamerican nephropathy kidney failure (odds ratio, 1.23; 95% confidence interval, 1.04 to 1.44; P=0.02). Compared with 16 matched healthy controls, Mesoamerican nephropathy kidney failure was significantly associated with exposure to paraquat and agrochemicals. Paraquat-treated male mice developed kidney failure and tubulointerstitial nephritis consistent with Mesoamerican nephropathy. Organic cation transporter-2 expression was higher in male kidneys versus female kidneys. Paraquat treatment increased organic cation transporter-2 expression and decreased multidrug and toxin extrusion 1 expression in male kidneys; similar results were observed in the kidneys of Nicaraguan patients with Mesoamerican nephropathy.ConclusionsExposure to agrochemicals is associated with Mesoamerican nephropathy, and chronic exposure of mice to paraquat, a prototypical oxidant, induced kidney failure similar to Mesoamerican nephropathy.

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“…The renal mRNA expression of HO-1 was measured, which has anti-inflammatory effects and is protective against kidney injury ( Courtney and Maxwell, 2008 ; Srivastava et al., 2020 ). We observed in both WT and SBP-1 KO infected mice a significant increase in the renal expression of HO-1 compared to the control group ( Figure 5D ).…”

Section: Resultsmentioning

confidence: 99%

Experimental malaria-associated acute kidney injury is independent of parasite sequestration and resolves upon antimalarial treatment

Possemiers

Pollenus²,

Prenen³

et al. 2022

Front. Cell. Infect. Microbiol.

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Malaria remains a important global disease with more than 200 million cases and 600 000 deaths each year. Malaria-associated acute kidney injury (MAKI) may occur in up to 40% of patients with severe malaria and is associated with increased mortality. Histopathological characteristics of AKI in malaria are acute tubular injury, interstitial nephritis, focal segmental glomerulosclerosis, collapsing glomerulopathy and glomerulonephritis. We observed that C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) develop MAKI in parallel with malaria-associated acute respiratory distress syndrome (MA-ARDS). MAKI pathology was associated with proteinuria, acute tubular injury and collapse of glomerular capillary tufts, which resolved rapidly after treatment with antimalarial drugs. Importantly, parasite sequestration was not detected in the kidneys in this model. Furthermore, with the use of skeleton binding protein-1 (SBP-1) KO PbNK65 parasites, we found that parasite sequestration in other organs and its subsequent high parasite load are not required for the development of experimental MAKI. Similar proteinuria, histopathological features, and increases in kidney expression of interferon-γ, TNF-α, kidney injury molecule-1 (KIM-1) and heme oxygenase-1 (HO-1) was observed in both infected groups despite a significant difference in parasite load. Taken together, we introduce a model of experimental AKI in malaria with important similarities to AKI in malaria patients. Therefore, this mouse model might be important to further study the pathogenesis of AKI in malaria.

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Protective role of HO‐1 against acute kidney injury caused by cutaneous exposure to arsenicals

Cited by 10 publications

References 64 publications

Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

Potential Mechanisms Involved in Chronic Kidney Disease of Unclear Etiology

Experimental malaria-associated acute kidney injury is independent of parasite sequestration and resolves upon antimalarial treatment

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