Gender difference in arsenic biotransformation is an important metabolic basis for arsenic toxicity

Muhetaer, Maihaba; Yang, Mei; Xia, Rongxiang; Lai, Yuanyan; Wu, Jun

doi:10.1186/s40360-022-00554-w

Cited by 21 publications

(12 citation statements)

References 45 publications

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“…[24] Using an animal model, researchers linked the effect of patient gender on As metabolism to different epigenetic regulations that are distinguishable between males and females. [25] In the present study, male and female patients did not have signi cant differences in Al and As serum levels, which means that gender does not cause signi cant changes in Al and As metabolism in hemodialysis patients.…”

Section: Discussionsupporting

confidence: 44%

Maintenance hemodialysis exacerbate aluminum and arsenic toxicity in chronic kidney disease patients Running title: Aluminum and Arsenic toxicity in hemodialysis patients

Absalan,

Momeni,

Salehi

et al. 2024

Preprint

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Background Maintenance hemodialysis (MHD) is the most effective interventional therapy for patients with chronic kidney disease (CKD). Our aim was to investigate the serum levels of aluminum (Al) and arsenic (As) in CKD patients. Methods A total of 29 CKD patients receiving MHD were surveyed for selected biochemical, and dialysis quality indices. Serum Al and As levels were measured before and after MHD. Statistical analyses included independent samples t-test or Mann-Whitney, Kaplan-Meier, Pearson, or Spearman's rho correlations. Results All patients (n = 29; 100%) had detectable levels of arsenicosis (cut-off = 1µg/L) both before hemodialysis (BFH) (mean ± SD = 7.58 ± 1.99µg/L) and after hemodialysis (AFH) (mean ± SD = 8.61 ± 1.82µg/L). Al toxicity was detected (cut-off = 10µg/L) in 24 (82.8%) individuals BFH (mean ± SD = 25.6 ± 15.61µg/L) and in 28 (96.6%) patients AFH (mean ± SD = 30.08 ± 15.18µg/L). The mean age of the patients was 60.41 ± 15.30 years (11 females and 18 males). Al BFH was positively correlated with its AFH level (R = 0.765; p = 0.000), but this was not true for As (R = 0.296; p = 0.167). Serum phosphate was negatively correlated with Al BFH (R=-0.547; p = 0.008). MHD was not efficient in eliminating Al and As from blood circulation when we compared their concentrations in inlet and outlet dialysis apparatus samples. Conclusions Our findings suggest that CKD patients undergoing MHD are at risk for overt Al and As toxicity, which highlights the importance of regularly monitoring toxic elements in these patients. Treatment with chelators and redefinition of cut-off points for Al and As blood levels in hemodialysis patients may be necessary.

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Section: Discussionsupporting

confidence: 44%

Maintenance hemodialysis exacerbate aluminum and arsenic toxicity in chronic kidney disease patients Running title: Aluminum and Arsenic toxicity in hemodialysis patients

Absalan,

Momeni,

Salehi

et al. 2024

Preprint

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“…Several studies have demonstrated a better methylation capacity in women than in men, and the sex differences in the metabolic biotransformation of arsenic seem to play a part in the generally lower arsenic toxicity in females than in males. [3][4][5] Improved female methylation of As can be partially explained by estrogen-dependent upregulation of the synthesis of choline as a critical cofactor in the generation of SAME, the essential methyl donor in the oxidative methylation of iAs. 4 The lower female consumption of SAME for their reduced creatinine synthesis (Sup Tbl 3) will further add to this effect.…”

Section: Sex Differences In Renal Arsenic Excretionmentioning

confidence: 99%

“…An animal study demonstrated less pronounced decreases in SAME activity after high-dose exposure to arsenate (iAsV) or arsenite (iAsIII) compared to low-or medium-dose exposure in female vs. male rats. 5 Thus, women could dispose of more SAME as an essential cofactor for oxidative methylation of iAs. Apart from the evident advantages in methylation, females also seem to exhibit improved renal antioxidative defense mechanisms due to higher expression of protective enzymes such as eNOS, Metallothionein, Mn-SOD, or Carbon-Anhydrase (Sup Tbl 3), favoring more efficient oxidative methylation of iAs.…”

Section: Sex Differences In Renal Arsenic Excretionmentioning

confidence: 99%

Non-linear dilution adjustment of exemplary urine arsenic Part II: Sex- and Age-specific Differences

Carmine

2023

Preprint

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Background In the first part of this study, a variable power-functional creatinine correction (V-PFCRC), normalizing results to 1 g/L creatinine (uCR), was established for total weight spot-urinary arsenic (TWuAs) as an adequate method of urinary dilution. In this second part, the impact of age and sex on TWuAs, V-PFCRC functions, and fluid regulation was investigated in the identical dataset of the first part based on a comprehensive literature review. Methods All samples with age indication, uAsUC ≤ 500 mg/L, and uCR < 4.5 g/L (n=5585, females n= 2967, males n = 2618) were classified into seven age groups, for which sex-aggregate and disaggregate means ± SEs, medians, and ICRs were calculated for uCR and TWuAs in uncorrected (uAsUC), classical CR corrected (CCRC, uAsC), and V-PFCRC (uAsN) results mode. In addition, Pearson correlation analyses were performed for uCR and TWuAs with age. In addition, sex-aggregated and disaggregated V-PFCRC functions were compared between three numerically similar age groups. Finally, the efficacy of creatinine correction error (CRCE) compensation was assessed by simple power-functional regression analysis (PFRA) in both sexes and seven age bands. Findings The clear male dominance of uAsUC (p < 0.001) in aggregate age data and all five adult subgroups separately was inverted by CCRC (uAsC, p = 0.011) and neutralized by V-PFCRC (uAsN, p = 0.19). Children and adolescents did not exhibit significant sex variations in TWuAs or uCR. A continuous rise in TWuAs with age from adolescence to the beginning of the seventh decade of life was observed in uAsUC, uAsC, and uAsN (0.28 µg/1 g uCR/year). Conversely, TWuAs decreased from childhood to adolescence and in the highest age group. Pearson analysis for all patients between 14 - 72 years and uAsUC ≤ 500 mg/L revealed significant weak positive correlations (p < 0.001) between TWuAs and age. The log curves between the coefficient a (= uAsN) and exponent b ran higher in younger men and both sexes among seniors, in broad analogy with reportedly higher baseline renal vasopressor activities of angiotensin II (ATII) and arginine vasopressin (AVP, V1) in these subgroups. The efficacy of V-PFCRC was established based on minimized residual biases of uCR on uAsN in both sexes and all seven age bands (R2 0.0029 - 7.0E-09). Interpretation Sex differences in uAsUC and uAsC are primarily attributable to distinct urinary dilution and thus are compensated by V-PFCRC. In contrast, age-dependent increases in TWuAs, evident in all results modes, are genuine and should be further accounted for in exposure studies and normal range determinations. While sex and age affect V-PFCRC formulas analog to baseline vasopressor activities of ATII/AVP, they only negligibly affect the correction validity. Adequate perception of power-functional relations between uCR and uAsUC alone, even neglecting these minor sex- and age-specific differences in V-PFCRC correction formulas, results in substantial improvement of dilution adjustment.

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Section: Sex Differences In Renal Arsenic Excretionmentioning

confidence: 99%

Section: Sex Differences In Renal Arsenic Excretionmentioning

confidence: 99%

The Role of Age and Sex in Non-linear Dilution Adjustment of Spot Urine Arsenic

Carmine¹

2023

Preprint

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Background In the first part of this study, a variable power-functional creatinine correction (V-PFCRC), normalizing results to 1 g/L creatinine (uCR) was established for total weight spot-urinary arsenic (TWuAs) as an adequate method of urinary dilution. In this second part, the impact of age and sex on TWuAs, V-PFCRC functions, and fluid regulation was investigated in the identical dataset of the first part based on a comprehensive literature review. Methods All samples with age indication, uAsUC <= 500 mcg/L and uCR < 4.5 g/L (n=5585, females n= 2967, males n = 2618) were classified into seven age groups, for which sex-aggregate and disaggregate means (SEs), medians, and ICRs were calculated for uCR and TWuAs in uncorrected (uAsUC), classical CR corrected (CCRC, uAsC), and V-PFCRC (uAsN) results mode. In addition, Pearson correlation analyses were performed for uCR and TWuAs with age. In addition, sex-aggregated - and disaggregated V-PFCRC functions were compared between three numerically similar age groups. Finally, the efficacy of creatinine correction error (CRCE) compensation was assessed by simple power-functional regression analysis (PFRA) in both sexes and seven age bands. Findings The clear male dominance uAsUC (p < 0.001) in aggregate age data and all five adult subgroups separately was found inverted by CCRC (uAsC, p = 0.011) and neutralized by V-PFCRC (uAsN, p = 0.19). Children and adolescents did not exhibit significant sex variations of TWuAs or uCR. A continuous rise of TWuAs with age from adolescence to the beginning of the seventh decade of life was observed in uAsUC, uAsC, and uAsN (0.28 mcg/1g uCR/year). Conversely, TWuAs decreased from childhood to adolescence and in the highest age group. Pearson analysis for all patients between 14 - 72 years and uAsUC < 500 mcg/L revealed significant weak positive correlations (p < 0.001) between TWuAs and age. The log curves between the coefficient a (= uAsN) and exponent b ran higher in younger men and both sexes among seniors, in broad analogy with reportedly higher baseline renal vasopressor activities of Angiotensin II (ATII) and Arginine-Vasopressin (AVP, V1) in these subgroups. The efficacy of V-PFCRC was established based on minimized residual biases of uCR on uAsN in both sexes and all seven age bands (R2 0.0029 - 7.0E-09). Interpretation Sex differences in uAsUC and uAsC are primarily attributable to differentiate urinary dilution and thus are compensated by V-PFCRC. In contrast, age-dependent increases of TWuAs, evident in all results modes, are genuine and should be further accounted for in exposure studies and normal range determinations. While sex and age affect V-PFCRC formulas analog to baseline vasopressor activities of ATII/AVP, they only negligibly affect the correction validity. Adequate perception of power-functional relations between uCR and uAsUC alone, even neglecting these minor sex- and age-specific differences in V-PFCRC correction formulas, results in substantial improvement of dilution adjustment.

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Gender difference in arsenic biotransformation is an important metabolic basis for arsenic toxicity

Cited by 21 publications

References 45 publications

Maintenance hemodialysis exacerbate aluminum and arsenic toxicity in chronic kidney disease patients Running title: Aluminum and Arsenic toxicity in hemodialysis patients

Maintenance hemodialysis exacerbate aluminum and arsenic toxicity in chronic kidney disease patients Running title: Aluminum and Arsenic toxicity in hemodialysis patients

Non-linear dilution adjustment of exemplary urine arsenic Part II: Sex- and Age-specific Differences

The Role of Age and Sex in Non-linear Dilution Adjustment of Spot Urine Arsenic

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