Effect of copper chloride on adrenocortical activities in adult and immature male rats.
01 Mar 2002-Environmental Toxicology and Pharmacology (Elsevier)-Vol. 11, Iss: 2, pp 79-84
TL;DR: Intraperitoneal injection of copper chloride at the dose of 2000 μg/kg per day and higher doses for 26 days resulted in significant rise in adrenal weight, adrenal Δ(5)-3β hydroxysteroid dehydrogenase (HSD) activity and serum corticosterone level in both adult and immature male rats.
Abstract: Although copper is an important biological trace element required for normal metabolism, occupational exposure to copper in different industrial workers may result in abnormal rise in plasma copper level which can bring about adverse effects. Intraperitoneal injection of copper chloride at the dose of 2000 μg/kg per day and higher doses for 26 days resulted in significant rise in adrenal weight, adrenal Δ(5)-3β hydroxysteroid dehydrogenase (HSD) activity and serum corticosterone level in both adult and immature male rats, while 1000 μg/kg per day dose for 26 days duration did not significantly alter the adrenocortical activities and adrenal weight in adult rats. On the contrary, the latter lower dose caused a significant decrease in adrenal Δ(5) 3β HSD activity and serum corticosterone level in immature male rats.
TL;DR: It is suggested that copper has got a dose-dependent effect on testicular steroidogenic enzyme activity and stimulation of testicular spermatogenesis and serum testosterone and LH level in maturing male rats.
Abstract: Background: Copper is essential as a trace element for metabolic processes. Exposure to copper in industries develops toxicity among the workers. Previous findings on adverse effects of copper on male reproductive function in adult albino rats led to investigate the effects of this metal on reproductive function of maturing male rats in the present experiment. Methodology: To study these effects, immature (30 to 35 days old) Wistar strain albino rats weighing about 50-60 g were treated intraperitoneally with copper chloride at doses of 1000, 2000 and 3000 µg/kg body weight/day for 26 days. Result: Significant fall in accessory sex organ weight and inhibition of testicular 17β-hydroxysteroid dehydrogenase activity along with degeneration of testicular growing spermatogenic cells and reduction in serum testosterone, FSH and LH level were observed at the doses of 2000 and 3000µg/kg/day. On the other hand, at the dose of 1000 µg/kg/day significant increase in testicular steroidogenic enzyme activity and stimulation of testicular spermatogenesis along with rise in serum testosterone and LH level were observed, though no significant change was observed in serum FSH level. This suggests that copper has got a dose-dependent effect on testicular steroidogenesis and spermatogenesis and serum testosterone and LH level in maturing male rats.
TL;DR: In this article , the effects of copper exposure for 30 days on blood pressure (BP) and cardiac contractility and the putative involvement of nitric oxide (NO) and reactive oxygen species were investigated.
Abstract: Copper is an essential factor for the body's homeostasis. However, excess copper compromises organic functions.We investigated the effects of copper exposure for 30 days on blood pressure (BP) and cardiac contractility and the putative involvement of nitric oxide (NO) and reactive oxygen species.Wistar rats (12 weeks old, 280 g) were randomized to the treated group that was exposed for 30 days to copper (2000 μg/kg/day CuCl2) and the control (Ct) group that received intraperitoneal saline (0.9%).The blood concentration of copper was ~1.26 μg/mL in the copper-exposed group and ~0.024 μg/mL in the Ct group. The main metal accumulations occurred in the liver and kidneys. Copper exposure increased systolic BP (Cu: 141 ± 3 mmHg; Ct: 133 ± 3 mmHg) (tail cuff method), left ventricular systolic pressure and papillary muscle force. Calcium release from the sarcoplasmic reticulum was reduced. The contractile response to Ca2+ was increased by copper, and the effect was not altered by L-NAME. Copper increased contractions dependent on sarcolemmal Ca2+ influx, and this effect was not altered by L-NAME. The percentage response to isoproterenol decreased in the copper-exposed group, but L-NAME did not alter this reduction. Papillary force development at the peak and plateau of tetanic contractions also increased after copper exposure, but this effect was not altered by L-NAME. In situ detection of OH local production increased.Copper increased BP and cardiac force, increased Ca2+ inflow, reduced Ca2+ reuptake by the sarcoplasmic reticulum, and increased OH local production. Copper exposure at doses considered tolerable affects cardiac contractility.
21 May 2020-Journal of Environmental Science and Health Part A-toxic\/hazardous Substances & Environmental Engineering
TL;DR: The presented data suggest that copper has detrimental effects on sexual steroid hormones and consecutively on reproductive physiology.
Abstract: Copper is an environmental risk factor, which has various effects on reproductive endocrinology. In this study human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biologica...
TL;DR: Copper oxide nanoparticles may interfere with the secretion of gonadotropins and testosterone and ultimately lead to a disruption of the spermatogenesis process in male rats.
Abstract: Background and Objective: Copper oxide nanoparticles with unique properties have numerous biological applications with probably toxicity. This study was conducted to determine the toxicity of copper oxide nanoparticles on the pituitary-gonadal axis and spermatogenesis in male rats. Methods: In this experimental study, 40 male Wistar rats were randomly allocated into 4 groups including control group and three intervention groups which receiving the cancentration of 10, 20 and 30 mg/kg of copper oxide nanoparticles 5 times intra-peritoneally, respectively. Blood sampling was collected first day and 15 days after the last injection. Level of testosterone, FSH and LH were measured by ELISA method. After anesthesia and dissection of mice in each group, tissue sections of testis were prepared and stained with hematoxylin-eosin. Morphological status of spermatogenesis process and counting of types of cells (spermatogonium, spermatocyte and spermatid) were studied by optical microscope. Results: In the first day of blood collection, a significant increase in LH and FSH level was observed at concentrations of 10 and 30 mg/kg, respectively. Also, Testosterone and FSH level decreased significantly reduced at 10 mg/kg/bw concentration compared to control (P<0.05). In 15 days after of the last injection, level of testosterone (P<0.05) and LH (P<0. 05) significantly increased in concentrations of 10 and 30 mg/kg/bw respectively. Also, there was a significant reduction in level of FSH in the concentration of 10 mg/kg/bw (P<0.05). The examination of testis tissue sections showed a significant decrease (P<0.05) in density and number of cell types (spermatogonium, spermatocyte and spermatid) and anomalies in the spermatogenesis process, in a dose-dependent manner. The most disturbances was seen at a concentration of 30 mg/kg/bw of copper oxide nanoparticles. Conclusion: Copper oxide nanoparticles may interfere with the secretion of gonadotropins and testosterone and ultimately lead to a disruption of the spermatogenesis process.
TL;DR: Over the 10 years, 11 beta-HSD has progressed from an enzyme merely involved in the peripheral metabolism of cortisol to a crucial pre-receptor signaling pathway in the analysis of corticosteroid hormone action.
Abstract: In mammalian tissues, at least two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyze the interconversion of hormonally active C11-hydroxylated corticosteroids (cortisol, corticosterone) and their inactive C11-keto metabolites (cortisone, 11-dehydrocorticosterone). The type 1 and type 2 11 beta-HSD isozymes share only 14% homology and are separate gene products with different physiological roles, regulation, and tissue distribution. 11 beta-HSD2 is a high affinity NAD-dependent dehydrogenase that protects the mineralocorticoid receptor from glucocorticoid excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of apparent mineralocorticoid excess in which cortisol acts as a potent mineralocorticoid. By contrast, 11 beta-HSD1 acts predominantly as a reductase in vivo, facilitating glucocorticoid hormone action in key target tissues such as liver and adipose tissue. Over the 10 years, 11 beta-HSD has progressed from an enzyme merely involved in the peripheral metabolism of cortisol to a crucial pre-receptor signaling pathway in the analysis of corticosteroid hormone action. This review details the enzymology, molecular biology, distribution, regulation, and function of the 11 beta-HSD isozymes and highlights the clinical consequences of altered enzyme expression.
TL;DR: The results suggest that the main active species causing DNA damage are more likely copper-peroxide complexes, with similar reactivity to singlet oxygen and/or hydroxyl radical rather than hydroxym free radical.
Abstract: Site-specific DNA damage by Cu(II) plus H2O2 was investigated by a DNA-sequencing technique Cu(II) plus H2O2 induced strong DNA cleavage even without piperidine treatment Piperidine-labile sites were induced frequently at thymine and guanine residues and rarely at adenine residue A Cu(I)-specific chelating agent, bathocuproine, inhibited the DNA damage Neither ethanol nor mannitol inhibited it Of alcohols, tert-butyl alcohol, having relatively low reactivity to hydroxyl free radical, inhibited the DNA damage most strongly Sodium azide and 1,4-diazobicyclooctane completely inhibited cleavages at residues of the bases other than guanine Tris inhibited the DNA damage The enhancing effect of D2O on DNA damage was not observed ESR studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) showed that the hydroxyl radical adduct of DMPO was formed during the reaction of Cu(II) with H2O2, and that the addition of sodium formate produced the CO2- radical adduct of DMPO more efficiently than expected ESR studies showed that the nitroxide radical was formed from 2,2,6,6-tetramethyl-4-piperidone in the presence of Cu(II) plus H2O2, indicating the formation of singlet oxygen or its equivalent The effects of scavengers on DNA damage have considerable correlation with the effects of scavengers on the nitroxide radical production and DMPOOH formation The results suggest that the main active species causing DNA damage are more likely copper-peroxide complexes, with similar reactivity to singlet oxygen and/or hydroxyl radical rather than hydroxyl free radical
TL;DR: Testosterone replacement lowered both ACTH content and adrenal weight to control levels and estradiol administration increased it further, together with Gonadectomy and Adrenalectomy together, which increased pituitary ACTH Content.
Abstract: Gonadectomy in male rats impaired growth but increased pituitary and adrenal weight and adrenal RNA and DNA content. Pituitary ACTH content increased also. Testosterone replacement lowered both ACTH content and adrenal weight to control levels. Estradiol administration increased pituitary ACTH without a further increment in adrenal weight. Gonadectomy and adrenalectomy together increased pituitary ACTH content compared with adrenalectomy alone. Under these conditions, testosterone replacement reduced pituitary ACTH and estradiol administration increased it further. Plasma corticosterone (Cpd. B) concentrations in castrated males at rest, after stress or after ACTH injection did not differ from those observed in intact controls. Biological half-life in vivo was shortened and hepatic inactivation of steroid in vitro was increased. Steroid production by adrenal slices in vitro was diminished by castration, and the output of steroid in adrenal venous blood also decreased. Increased steroid secretion was produ...