Reactive oxygen species and male reproductive hormones

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility

<i>In vitro </i>stimulation of chick brain lipid peroxidation by aluminium, and effects of tiron, EDTA and some antioxidants

1231-1235In vitro effect of aluminium (Al) on Fe2+-induced lipid peroxidation (LPX) in various subcellular fractions from the cerebral hemispheres (CH) of 7- and 30-day old chicks was studied. Stimulation of Fe2+-induced LPX by Al was observed to be the highest in microsomal fraction. The magnitude of elevation of Fe2+-induced LPX in various subcellular fractions of brain showed age related variation. Of the six chemicals tested for their influence on Al-induced lipid peroxidation, both doses of 1,2-dihydroxybenzene-3,5-disulphonic acid disodium salt (Tiron), ethylene diamine tetra acetic acid disodium salt (EDTA), and ascorbic acid prevented the Al-induced LPX in crude homogenates of the CH, whereas only at a higher dose inhibition by 1,4-diazabicyclo (2.2.2.) octan (DABCO) was observed. On the contrary, mannitol and dimethyl sulfoxide did not inhibit the induction of LPX by Al in crude homogenate. The effect of test chemicals on Al-induced LPX in both the ages of chick tissue was almost similar. The results suggest that Al further augments Fe2+-induced LPX in various compartments of the cell due to generation of free radicals. The results also showed that Tiron, EDTA and antioxidants, such as ascorbic acid and DABCO can prevent LPX induced by Al

Induction and properties of pyruvate kinase of the cerebral hemisphere of rats of various ages

The induction of pyruvate kinase (ATP: pyruvate 2-O phosphotransferase, EC 2.7.1.40; PK) by estradiol or testosterone in the cerebral hemisphere of male and female rats of different ages was studied. There is a marked decrease in the activity of the enzyme of normal male and female rats with increasing age. Orchiectomy decreases its activity in young and old rats, but not in adult rats. Ovariectomy decreases its activity significantly in all the ages. Estradiol (50&#956;g/100g body wt.) induces its activity in castrated male and female rats, but its effect is greater in female rats. A higher dose of estradiol (100&#956;g/100g body wt.) has age- and sex-dependent induction. Testosterone (50 and 100&#956;g/100g body wt.) has very little effect on its activity in castrated male and female rats of the three ages. The Km values for PEP and ADP, and the Kt values for ATP and l-phenylalanine for the partially purified enzyme of the cerebral hemisphere of normal young and old rats are the same. Preincubation of the enzyme with l-alanine reverses the l-phenylalanine induced inhibition. The concentration of l-alanine required for this effect is the same for both ages. The concentration of Mg2+ required to reverse the inhibitory effect of ATP is the same for young and old rats. Estradiol and testosterone added directly to the incubation mixture do not have any effect on the enzyme activity. These data suggest that the nature of the enzyme molecule does not change with age, but that its induction properties change with age

Rat testicular mitochondrial antioxidant defence system and its modulation by aging

Accumulation of oxidative damage caused by reactive oxygen species (ROS) underlies fundamental changes found during aging. In the present study, age related effect on testicular mitochondrial oxidant generation and antioxidant defence profile was investigated in Wistar rats at 3 months (young adults), 12 months (old adults) and 24 months (senescent animals) of age. Mitochondrial oxidative stress parame- ters viz., lipid peroxidation (LPx), protein carbonylation, hydrogen peroxide (H 2 O 2 ) generation and activ- ities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), levels of total, oxidized (GSSG) and reduced glutathione (GSH) were studied to find out their roles in mainte- nance of mitochondrial glutathione redox pool as a function of age. Increased levels of LPx, H 2 O 2 and decreased GSH content accompanied by a decline in activities of SOD, GPx and GR with advancing age suggest that antioxidant defense profile of testicular mitochondria exhibit age related alterations which might play a critical role in regulating physiological functions of the testis such as steroidogenesis and spermatogenesis

A modified spectrophotometric assay of superoxide dismutase using nitrite formation by superoxide radicals

201-204A Simple inexpensive colorimetric assay system for SOD is reported. The method involves generation of superoxide radical by photoreduction of riboflavin and its detection by nitrite formation from hydroxylamine <span style="font-size:14.0pt; font-family:HiddenHorzOCR;mso-bidi-font-family:HiddenHorzOCR">hydrochloride at 543 nm. The method is more sensitive than the NBT method and less sensitive than the NADH method. </span

<span style="font-size:14.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#323232;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">Effects <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">of hypothyroidi<span style="font-size:14.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#484848;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">s<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">m induced by 6-n-propylthiouracil <span style="font-size: 14.0pt;line-height:115%;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";color:#323232;mso-ansi-language:EN-IN;mso-fareast-language: EN-IN;mso-bidi-language:HI" lang="EN-IN">and <span style="font-size:14.0pt; line-height:115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">its rever<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#484848;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">sa<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#0C0C0C;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">l <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">by T_{<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#5F5F5F;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">3</span>}<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#5F5F5F;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN"> <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">on rat heart <span style="font-size:14.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#323232;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">s<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#0C0C0C;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">up<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#323232;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">eroxide <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">di<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#484848;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">s<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">muta<span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#484848;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">se, <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">catalase <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#323232;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">and <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">lipid<b> </b>peroxidation</span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span></span>

846-849The present study critically evaluates the effects of hypothyroid and hyperthyroid states on lipid peroxidation and two enzymes of active oxygen metabolism, namely superoxide dismutase (SOD) and catalase (CAT) in the rat heart mitochondrial and post-mitochondrial fractions. Lipid peroxidation, an index of oxidative stress, was elevated in the heart tissue in hypothyroid state but reduced upon T3 supplementation. Hyperthyroidism registered increased SOD activity in post-mitochondrial fraction. Mitochondrial SOD activity was reduced in hypothyroid state which was further reduced by T3administration. In contrast, different thyroid states had no effect on catalase activity in the mitochondrial fraction. The hypothyroid State however, significantly augmented catalase activity in post-mitochondrial fraction. The results suggest that the antioxidant defence status of cardiac tissue is well modulated by thyroid hormone

Kinetics and mechanism of reduction of ferricytochrome c by glutathione and L-cysteine: A comparative study

37-40The kinetics and mechanism of the reduction of ferricytochrome c [Cyt c(III)] by substrates namely glutathione (GSH) and L-cysteine (L-cys) have been investigated spectrophotometrically employing [substrate]T >> [Cyt c(III)]T. The reaction exhibits first order dependence in [substrate]T and [Cyt c(III)]T. The pseudo-first order rate constant increases with an increase in pH, indicating that the conjugate base form of the HCyt c(III) is a better oxidant than the parent HCyt c(III). The electron transfer rate constants between the oxidants and GSH for both the k₁ and k₂ paths are found to be greater than that with L-cysteine. Hence, GSH is a better reductant of Cyt c(III) as compared to L-cysteine. A suitable mechanism has been proposed on the basis of experimental findings. The deprotonation constant for HCyt c(III) and the second order rate constants of k₁ and k₂ paths for the present reaction at 25ºC have been determined

Investigating the Conformational Structure and Potential Site Interactions of SOD Inhibitors on Ec-SOD in Marine Mud Crab Scylla serrata: A Molecular Modeling Approach

© 2015, International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg. Superoxide dismutases (SODs) act as a first line of the enzymatic antioxidant defense system to control cellular superoxide anion toxicity. Previously, several inhibitors have been widely identified and catalogued for inhibition of SOD activity; however, still the information about the mechanism of interaction and points toward the inhibitor interactions in structures of SODs in general and in extracellular (Ec)-SOD in particular is still in naive. In the present research, we present an insight to elucidate the molecular basis of interactions of SOD inhibitors with Ec-SOD in mud crab Scylla serrata using molecular modeling and docking approaches. Different inhibitors of SOD such as hydrogen peroxide ( H 2O2) , potassium cyanide, sodium dodecyl sulfate (SDS), β-mercaptoethanol and dithiocarbamate were screened to understand the potential sites that may act as sites for cleavage or blocking in the protein. SOD–SDS and SOD - H 2O2 complex interactions indicate residues Pro72 and Asp102 of the predicted crab Ec-SOD as common targets. The GOLD result indicates that Pro72, Asp102 and Thr103 are commonly acting as the site of interaction in Ec-SOD of S. serrata with SOD inhibitors. For the first time, the results of this study provide an insight into the structural properties of Ec-SOD of S. serrata and define the possible involvements between the amino acids present in its active sites, i.e., in the regions from 70 to 84 and from 101 to 103 and different inhibitors