Suppression of uric acid generation and blockade of glutathione dysregulation by L-arginine ameliorates dichlorvos-induced oxidative hepatorenal damage in rats

Saka, W.A.; Akhigbe, R.E.; Abidoye, A.O.; Dare, O.S.; Adekunle, Adebayo Oluwafemi

doi:10.1016/j.biopha.2021.111443

Cited by 31 publications

(16 citation statements)

References 40 publications

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“…The improved circulating NO level exerts immune-modulatory effects and inhibits the migration of monocyte and lymphocytes to the endothelium, thus maintaining penile endothelial homeostasis [ 45 ] and promoting penile reflexes. Also, arginine-driven NO increase possibly enhanced tissue perfusion, promoting their secretory function [ 13 ], and resulting in improved testosterone levels. It is also not unlikely that arginine-led NO rise activated soluble guanylyl cyclase that converts guanosine triphosphate to cGMP, which in turn activates protein kinase G to promote vasorelaxation and penile smooth muscle relaxation [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…On the other hand, L-arginine is a semi-essential proteinogenic amino acid that is synthesized endogenously; however, exogenous intake as a diet supplement contributes to the body’s supply and militates against alterations in its metabolism [ 13 , 14 ]. The intake of arginine has been shown to increase its concentrations in the plasma and tissues [ 13 ]. Although data reporting the impact of L-arginine on male reproductive function is limited, it has been established as a substrate of nitric oxide (NO), thus by extension, up-regulates NO/cGMP signaling and promotes smooth muscle relaxation and vasodilatation [ 15 ] with likely positive impact on sexual function.…”

Section: Introductionmentioning

confidence: 99%

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L-Arginine reverses maternal and pre-pubertal codeine exposure-induced sexual dysfunction via upregulation of androgen receptor gene and NO/cGMP signaling

2022

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Background Although codeine has been reported to enhance sexual activity by improving penile reflexes, it has been shown to impair fertility indices. Also, codeine impairs ovarian steroidogenesis and folliculogenesis. Nonetheless, whether or not codeine exerts an epigenetic effect remains unclear. On the other hand, arginine has been speculated to enhance penile reflexes by upregulating NO/cGMP Signaling. Aim The study evaluated the effect of maternal codeine exposure and prepubertal codeine and arginine treatments on F1 male sexual function and fertility indices, as well as the outcome of F2 progenies. In addition, the epigenetic programming mechanism was also explored. Methods Forty three-week-old female rats were randomized into two groups (n = 20 rats/group); the control that received 0.5 ml of distilled water and the codeine-treated that received 5 mg/kg of codeine via gavage for eight weeks. Afterward, the female rats were paired for mating with sexually mature male rats. Rats were maintained on their pre-pregnancy treatments throughout pregnancy and lactation. FI progenies from each cohort (control and codeine-treated cohorts) were weaned at three weeks and randomized into four groups; the control, codeine-treated, L-arginine-treated (300mg/kg), and codeine + L-arginine-treated (n = 10 rats/group). Administration commenced a week post-weaning and lasted for eight weeks via gavage. Key findings Maternal codeine exposure did not alter body weight, but significantly reduced anogenital distance and anogenital index of F1 male offspring. Also, maternal codeine delayed preputial membrane separation, impaired male sexual competence, and penile reflexes of F1 male offsprings. These were associated with reduced dopamine, gonadotropins, and testosterone levels as well as suppressed expression of androgen receptor mRNA. In addition, maternal codeine downregulated NO/cGMP signaling, impaired fertility indices, and reduced the litter size, weight, and survival of F2 progenies. These alterations were observed to be aggravated by prepubertal codeine exposure but improved by prepubertal arginine treatment. Significance In conclusion, codeine programmed sexual dysfunction by suppressing the levels of dopamine and testosterone, as well as repressing the expression of androgen receptor mRNA. In addition, codeine-induced epigenetic reprogramming was expressed in the F2 offsprings as reduced litter size and weight, and survival rate. Notably, these observations were worsened by prepubertal codeine exposure, but dampened by prepubertal arginine treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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L-Arginine reverses maternal and pre-pubertal codeine exposure-induced sexual dysfunction via upregulation of androgen receptor gene and NO/cGMP signaling

2022

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“…The XOD inhibitory activities of peptides are partly attributed to tryptophan (Trp) residues due to the similar C6 and C5 ring structures of Trp, allopurinol and xanthine, 22,28 while treatment with arginine (Arg) alone suppresses uric acid generation. 29 However, GPAGPR and GPSGRP contain one Arg each and no Trp but still showed XOD inhibitory activities (Fig. 1C-F).…”

Section: Discussionmentioning

confidence: 93%

Novel anti-hyperuricemic hexapeptides derived from Apostichopus japonicus hydrolysate and their modulation effects on the gut microbiota and host microRNA profile

Fan

Huang

Lu³

et al. 2022

Food Funct.

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“…Increased concentrations of creatinine and urea in plasma or serum of rats after poisoning with OPs in different doses have been observed for many representatives of this group of chemicals, at different dates of observation and routes of administration. In particular, this has been described for methyl parathion at a dose of 0.56 mg/kg (1/25 LD50)/1 time/3 days p/o for 8 weeks [17]; soman at a single dose of 0.67 LD50 [39]; dichlorophos at aerosol ingestion at a dose of 98.5 g/m 3 with a daily exposure of 15 min for 28 days [40]; malathion at a dose of 75 mg/kg daily p/o for 7 days [41] and at a dose of 100 mg/kg daily p/o for 30 days [12]; diazinon once intraperitoneally in a dose of 100 mg/kg [10]; chlorpyrofos at a dose of 10 mg/kg combined with carbendazim at a dose of 50 mg/kg p/o for 7 days [42]; and some others. Thus, we can say that potential nephrotoxicity has been established for many OPs representatives if we take increased creatinine and urea concentrations as evidence of impaired renal function.…”

Section: Biochemical Aspects Of Pox Nephrotoxicitymentioning

confidence: 97%

Nephrotoxic Effects of Paraoxon in Three Rat Models of Acute Intoxication

Соболев

Sokolova

Jenkins

et al. 2021

IJMS

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The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specific effects. The present study was designed to investigate the nephrotoxic effects of paraoxon (O,O-diethyl O-(4-nitrophenyl) phosphate, POX) using three models of acute poisoning in outbred Wistar rats. In the first model (M1, POX2x group), POX was administered twice at doses 110 µg/kg and 130 µg/kg subcutaneously, with an interval of 1 h. In the second model (M2, CBPOX group), 1 h prior to POX poisoning at a dose of 130 µg/kg subcutaneously, carboxylesterase activity was pre-inhibited by administration of specific inhibitor cresylbenzodioxaphosphorin oxide (CBDP, 3.3 mg/kg intraperitoneally). In the third model (M3), POX was administered subcutaneously just once at doses of LD16 (241 µg/kg), LD50 (250 µg/kg), and LD84 (259 µg/kg). Animal observation and sampling were performed 1, 3, and 7 days after the exposure. Endogenous creatinine clearance (ECC) decreased in 24 h in the POX2x group (p = 0.011). Glucosuria was observed in rats 24 h after exposure to POX in both M1 and M2 models. After 3 days, an increase in urinary excretion of chondroitin sulfate (CS, p = 0.024) and calbindin (p = 0.006) was observed in rats of the CBPOX group. Morphometric analysis revealed a number of differences most significant for rats in the CBPOX group. Furthermore, there was an increase in the area of the renal corpuscles (p = 0.0006), an increase in the diameter of the lumen of the proximal convoluted tubules (PCT, p = 0.0006), and narrowing of the diameter of the distal tubules (p = 0.001). After 7 days, the diameter of the PCT lumen was still increased in the nephrons of the CBPOX group (p = 0.0009). In the M3 model, histopathological and ultrastructural changes in the kidneys were revealed after the exposure to POX at doses of LD50 and LD84. Over a period from 24 h to 3 days, a significant (p = 0.018) expansion of Bowman’s capsule was observed in the kidneys of rats of both the LD50 and LD84 groups. In the epithelium of the proximal tubules, stretching of the basal labyrinth, pycnotic nuclei, and desquamation of microvilli on the apical surface were revealed. In the epithelium of the distal tubules, partial swelling and destruction of mitochondria and pycnotic nuclei was observed, and nuclei were displaced towards the apical surface of cells. After 7 days of the exposure to POX, an increase in the thickness of the glomerular basement membrane (GBM) was observed in the LD50 and LD84 groups (p = 0.019 and 0.026, respectively). Moreover, signs of damage to tubular epithelial cells persisted with blockage of the tubule lumen by cellular detritus and local destruction of the surface of apical cells. Comparison of results from the three models demonstrates that the nephrotoxic effects of POX, evaluated at 1 and 3 days, appear regardless of prior inhibition of carboxylesterase activity.

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Suppression of uric acid generation and blockade of glutathione dysregulation by L-arginine ameliorates dichlorvos-induced oxidative hepatorenal damage in rats

Cited by 31 publications

References 40 publications

L-Arginine reverses maternal and pre-pubertal codeine exposure-induced sexual dysfunction via upregulation of androgen receptor gene and NO/cGMP signaling

L-Arginine reverses maternal and pre-pubertal codeine exposure-induced sexual dysfunction via upregulation of androgen receptor gene and NO/cGMP signaling

Novel anti-hyperuricemic hexapeptides derived from Apostichopus japonicus hydrolysate and their modulation effects on the gut microbiota and host microRNA profile

Nephrotoxic Effects of Paraoxon in Three Rat Models of Acute Intoxication

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