Creatinine Formation and Inorg-As Biotransformation: Influence of Trace Elements

Authors

• Uttam K Chowdhury Department of Molecular and Cellular Biology, The University of Arizona, Life Sciences South, Tucson, Arizona, 85721-0106, USA.

Abstract

Recently, a study showed that urinary creatinineconcentrations (mg/L) were positively and significantly correlated withAsconcentrations, expressed as μg/L in urine (UAs) for both females and males¹. Theurinary creatinine concentrations were also positively correlated with As concentrations expressed as μg/L in blood¹. Other researchers also reported that urinary creatinine concentrations werepositively correlated with UAs concentrations expressed asμg/L^2,3. These results suggest that creatinine may influence the release of arsenic from the body with unknown mechanisms or maybe there is a correlation between the formation of creatinine and arsenic metabolism. Chowdhury UK (2021)⁴ found the important results that adjustedurinary Se, Mn, and Hg concentrations expressed as ug/g crewere significantly and negatively correlated with urinarycreatinine for both sexes. He also found a statisticallysignificant and positive correlation between Mn and Hg in urinefor both females and males (data not shown). Other studies reportedthat the combination of Mn and Hg might be more injurious tothe brain, perhaps due to their synergistic effect⁵. The effect ofHg administered or exposed on renal dysfunction has beenreported^6-8. Selenium intoxication with selenite broth resultingin acute renal failure has also been reported⁹. Therefore, Se,Mn, and/ or Hg may have inhibitory effects in renal function andforming less creatinine when increasing Se, Mn, and/or Hgconcentrations.

Recently, a study showed that urinary creatinine concentrations (mg/L) were positively and significantly correlated with As concentrations, expressed as μg/L in urine (UAs) for both females and males¹. The urinary creatinine concentrations were also positively correlated with As concentrations expressed as μg/L in blood¹. Other researchers also reported that urinary creatinine concentrations were positively correlated with UAs concentrations expressed as μg/L^2,3. These results suggest that creatinine may influence the release of arsenic from the body with unknown mechanisms or maybe there is a correlation between the formation of creatinine and arsenic metabolism. Chowdhury UK (2021)⁴ found the important results that adjusted urinary Se, Mn, and Hg concentrations expressed as ug/g cre were significantly and negatively correlated with urinary creatinine for both sexes. He also found a statistically significant and positive correlation between Mn and Hg in urine for both females and males (data not shown). Other studies reported that the combination of Mn and Hg might be more injurious to the brain, perhaps due to their synergistic effect⁵. The effect of Hg administered or exposed on renal dysfunction has been reported^6-8. Selenium intoxication with selenite broth resulting in acute renal failure has also been reported⁹. Therefore, Se, Mn, and/ or Hg may have inhibitory effects in renal function and forming less creatinine when increasing Se, Mn, and/or Hg concentrations.

In Boeniger et al. (1993)¹⁰ reported that 15-20% of the creatinine in urine could occur by active secretion from the blood through the renal tubules, i.e., urinary creatinine is influenced by renal function, which could have some unclear function for arsenic methylation process. Researcher¹ reported that urinary creatinine concentrations were strongly and positively correlated with % DMA in urines. Therefore, DMA formation could be decreased when creatinine formation will be decreased. On the other hand, creatinine formation/concentrations could be decreased when Se, Mn, and/or Hg concentrations will be increased, i.e., DMA concentrations might be decreased. The results also confirmed the other findings that % DMA and the ratio of % DMA to % MMA were decreased with increasing Se, Mn, or Hg concentrations expressed as ug/g cre in urine^1,4. The correlation was stronger for males compared to females^1,4. These results suggest that maybe Mn and Hg are more potent inhibitor for MMA methyltransferase in males compared to females and producing less % DMA in males compared to females. Due to that more MMA (highly toxic) accumulated in tissues of males compared to females. Other researchers have been reported that Se and Hg decreased As methylation^11-14. They also suggested that the synthesis of DMA from MMA might be more susceptible to inhibition by Se(IV)¹⁴ as well as by Hg(II)^11,13 compared to the production of MMA from inorg- As(III). A possible molecular link between As, Se, and Hg has been proposed by Korbas et al. (2008)¹⁵. The identifying complexes between the interaction of As and Se, Se and Hg as well as As, Se, and Hg in blood of rabbit has been reported^15,16(Table 1).

Table 1. The identifying complexes between the interaction of As and Se, Se and Hg as well as As, Se, and Hg.

Some studies have also reported that Se supplementationdecreased the As induced toxicity^17,18.

The concentrations of urinary Se expressed as ug/L were negatively correlated with urinary % Inorg-As and positively correlated with % DMA¹⁹. These studies did not address the urinary creatinine adjustment. Other researchers suggested that Se and Hg decreased As methylation^11-14(Table 2). They also suggested that the synthesis of DMA from MMA might be more susceptible to inhibition by Se (IV)¹⁴ as well as by Hg (II)^11,13 compared to the production of MMA from Inorg-As (III). The inhibitory effects of Se and Hgwere concentration dependent^11-14.

Table 2. The impact of Se as well as Hg for As-induced toxicity and metabolism.

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