n-Butanol fraction of moringa seed attenuates arsenic intoxication by regulating the uterine inflammatory and apoptotic pathways.

The adverse effects of arsenic-chelating drugs make it essential to replace invasive chelating therapy with non-invasive oral therapy for arsenic poisoning. The goal of the current investigation was to determine whether the uterine damage caused by arsenization could be repaired by the n-butanol fraction of Moringa oleifera seed (NB). The rats were orally administered with arsenic (10 mg/kg BW) for the initial 8 days, followed by NB (50 mg/kg) for the next 8 days without arsenic. The probable existence of different components in NB was evaluated by HPLC-MS. Pro and anti-inflammatory indicators were assessed by RT-PCR and western blot. ESR-α was detected via immunostaining. Arsenic-exposed rats had significantly increased lipid peroxidation and decreased antioxidant enzyme activity, which were markedly reduced after NB treatment. Weaker ESR-α expression and distorted uterine histomorphology following arsenication were retrieved significantly by NB. Meaningful restoration by NB was also achieved for altered mRNA and protein expression of various inflammatory and apoptotic indicators. Molecular interaction predicted that glucomoringin and methyl glucosinolate of moringa interact with the catalytic site of caspase-3 in a way that limits its activity. However, NB was successful in restoring the arsenic-mediated uterine hypofunction. The glucomoringin and methyl glucosinolate present in n-butanol fraction may play a critical role in limiting apoptotic event in the arsenicated uterus.

Arsenic-induced uterine apoptotic damage is protected by ethyl acetate fraction of Camellia sinensis (green tea) via Bcl-2-BAX through NF-κB regulations in Wistar rats.

The non-invasive treatment strategy is indispensable to overcome the side effects of conventional treatment with chelating agents against arsenic. Presence of catechins and flavonoids in Camellia sinensis have potential antioxidant properties and other beneficial effects. The aim of the study was to explore the curative potential role of Camellia sinensis against uterine damages produced by sodium arsenite in mature albino rats. A dose of 10 mg of Camellia sinensis ethyl acetate (CS-EA) fraction/100 gm body weight was provided to the sodium arsenite-treated rats (10 mg/Kg body weight). LC-MS analysis was used for the detection of active component in CS-EA fraction. Enzymatic antioxidants analysis carried out by reproducible native gel technique. Hormones and some pro and anti-inflammatory markers were detected by ELISA, PCR, and western blot techniques respectively. Immunostaining was performed for the detection of estradiol receptor alpha. LC-MS analysis of CS-EA fraction ensured the presence of active tea polyphenol and tea catechin of which highest peak of epigallocatechin-3 gallate (EGCG) was obtained in this study. Significant elevations of lipid peroxidation end products followed by the diminution of antioxidant enzymes activities were noted in arsenicated rats which were capably retrieved by the treatment of CS-EA fraction. Post-treatment with CS-EA fraction meaningfully improved gonadotrophins and estradiol signalling in association with a highly expressing estradiol receptor-α (ERα) in the ovary and uterus followed by the maintenance of normal utero-ovarian histoarchitecture in arsenic fed rats. CS-EA fractioned treated group overturned the sodium arsenite driven higher expression of pro-inflammatory cytokines and proapoptotic markers along with a low level of anti apoptotic Bcl-2 expression and comparatively lower NF-κB signalling in the uterus via regulating IKK ß kinase mostly by EGCG of CS-EA fraction. However, ethyl acetate fraction of Camellia sinensis played a critical role in minimizing arsenic-mediated uterine hypo-function.

Involvement of metallothionein, homocysteine and B-vitamins in the attenuation of arsenic-induced uterine disorders in response to the oral application of hydro-ethanolic extract of Moringa oleifera seed: a preliminary study.

The painful invasive chelation therapy makes it challenging to continue the prolonged treatment against arsenic toxicity. Hence, the significance of the present preliminary investigation was to explore a noninvasive treatment strategy against sodium arsenite (As3+) by the use of a hydroethanolic extract of Moringa oleifera (MO) seed. Arsenic treatment (10 mg/kg body-weight) in animals showed significant level of oxidative stress as evidenced by increased serum levels of malondialdehyde (MDA), conjugated dienes (CD) and reduced level of non-protein thiol (NPSH). A significant diminution in the activities of enzymatic antioxidants was noted in As3+-treated rats. As3+ treatment showed a lengthy phase of metestrous in animals followed by significantly diminished ovarian steroidogenesis, increased ovarian follicular degeneration and distortion of uterine tissue histomorphology. In addition, there was a significant depletion of Vitamin-B9 (folate) and B12 following As3+ ingestion. The levels of circulating TNF-α, homocysteine (Hcy), uterine-IL-6, and liver metallothionein (MT-1) were significantly elevated in arsenic treated rats. MO at a dose of 100 mg/kg body-weight could successfully mitigate the uterine ROS generation by maintaining the uterine antioxidant status in As3+- treated rats. This seed extract prevented the deterioration of As3+-mediated ovarian-steroidogenesis and ovarian and uterine histoarchitecture significantly. B9 and B12 levels were also improved following the ingestion of the MO extract in arsenicated animals. Elevation of Hcy, TNF-α and IL-6 was also prevented by this MO seed extract in As3+-treated rats. A further increase of MT-1 level was achieved after MO ingestion in As3+-treated rats. Here, the alleviation of arsenic toxicity might involve via the regulation of the components of S-adenosine methionine (SAM) pool and MT-1.

Involvement of proinflammatory cytokines and metallothionein in the repairing of arsenic-mediated uterine tissue damage by curcumin.

Background Curcumin is extensively used as a therapeutic intervention for treating several ailments. The antioxidant curcumin has an anti-inflammatory and chelating property with arsenic to exhibit a strong therapeutic effect on reproductive organs. This study was undertaken to describe the protective effect of noninvasive administration of curcumin against sodium-arsenite-mediated uterine hazards in female Wistar rats. Methods Twenty-four female Wistar rats were randomly divided into four groups. The treatment was continued for 8 days and given orally sodium arsenite (10 mg/kg body weight) in combination with curcumin (20 mg/kg body weight). Results Our evaluation revealed that 8 days of sodium arsenite (10 mg/kg body weight) treatment reduced the activities of the uterine enzymatic antioxidants superoxide dismutase, catalase, and peroxidase. Blood levels of vitamin B12 and folic acid decreased followed by an increased serum lactate dehydrogenase, homocysteine level, and hepatic metallothionein-1 in arsenic-treated rats. Necrosis of uterine tissue along with the disruption of ovarian steroidogenesis was marked in arsenic-treated rats with an upregulation of uterine NF-κB and IL-6 along with a raised level of serum TNF-α. Oral administration of curcumin (20 mg/kg body weight/day) in arsenic-treated rats significantly reinstated these alterations of the antioxidant system followed by an improvement of ovarian steroidogenesis and the circulating level of B12 and folate along with the downregulation of serum homocysteine, metallothionein-1, and cytokines. Conclusions The findings of this study clearly and strongly elucidated that arsenic-induced oxidative stress in uterus is linked to an alteration of inflammation-signaling biomarkers and these have been protected through the co-administration of curcumin due to its anti-inflammatory, free radical scavenging, and antioxidant activity by the possible regulation of an S-adenosine methionine pool.

Dietary CCPS from bitter gourd attenuates sodium arsenite induced female reproductive ailments cum infertility in wistar rats: anti-inflammatory and anti-apoptotic role.

This investigation explored a dietary therapy of pectic polysaccharide (CCPS) (2 mg/ Kg BW) against female repro-toxicity and infertility triggered by sodium arsenite (As3+) (10 mg/ Kg BW) in Wistar rats. The isolated CCPS consists of D-galactose and D-methyl galacturonate with a molar ratio of 1: 4. FTIR spectral analysis of CCPS and CCPS- sodium arsenite (As3+) complex indicated a possible chelating property of CCPS in presence of binding sites (OH-/COOH) for As3+. Series of negatively charged galacturonate residues in CCPS provide better potential for cation chelation. CCPS significantly mitigated As3+ induced ovarian, uterine lipid peroxidation, and reactive oxygen species (ROS) generation by the restoration of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities. CCPS post-treatment enhanced ovarian steroidogenesis along with a restoration of normal tissue histoarchitecture in As3+ fed rats by regulating the estradiol receptor alpha (ER-α). CCPS suppressed anti-inflammatory properties effectively found since a down-regulation of NF-kappa B (NF-қB), pro-inflammatory tumor necrosis-α (TNF-α) and interleukin-6 (IL-6) were observed in arsenicated rats with CCPS. This study confirmed the up-regulation of uterine pro-apoptotic/ apoptotic proteins caspase-3, poly ADP ribose polymerase (PARP), proliferating cell nuclear antigen (PCNA), phospho p53 and Bax, followed by down-regulation of Bcl-2 and protein Kinase B (AKT) signaling pathway along with uterine tissue regeneration in As3+ exposed rats. Oral CCPS attenuated the above apoptotic expressional changes significantly and dietary CCPS ensured successful fertility with the birth of healthy pups in lieu of infertile condition in As3+ fed rats. Moreover, this study also supports that CCPS treatment attenuated the As3+ toxicity by modulating the S-adenosine methionine (SAM) pool components, B12, folate and homocysteine.

Association of Vitamin B12, Lactate Dehydrogenase, and Regulation of NF-κB in the Mitigation of Sodium Arsenite-Induced ROS Generation in Uterine Tissue by Commercially Available Probiotics.

Managing arsenic intoxication with conventional metal chelators is a global challenge. The present study demonstrated the therapeutic role of probiotics against arsenic-induced oxidative stress and female reproductive dysfunction. Sodium arsenite-treated (1.0 mg/100 g body weight) Wistar female rats were followed up by a post-treatment of commercially available probiotic mixture in powder form (0.25 mg/100 g body weight) orally. Rats that experienced arsenic ingestion showed a significant lessening in the activities of uterine superoxide dismutase (SOD), catalase activities, and the level of non-protein soluble thiol (NPSH) with a concomitant increase in malondialdehyde (MDA) and conjugated dienes (CD). Exposure to arsenic significantly lowered the levels of vitamin B12 and estradiol. Exposure to arsenic highly expressed the inflammatory marker and transcription factor NF-κB. Arsenic-mediated instability of these above parameters was controlled by the probiotics with a rebuilding of better function of anti-oxidant components. Besides its function in regulating endogenous anti-oxidant system, probiotics were able to augment the protection against mutagenic uterine DNA-breakage, necrosis, and ovarian-uterine tissue damages in arsenicated rats.

Attenuation of utero-toxicity, metabolic dysfunction and inflammation by soy protein concentrate in rats exposed to fluoridated water: consequence of hyperlipidemia in parallel with hypohomocysteinemia.

Lipid peroxidation and ROS generation are the pathogenesis of chronic fluoride toxicity, and its detrimental effects on human reproduction are noted drastically. The aim of the present study was to elucidate the defensive effects of soy protein concentrate (SPC) against sodium fluoride (NaF)-induced uterine dysfunction at biochemical and histological level. Rats were randomly distributed into four groups as control, NaF-treated (200 ppm), and SPC co-administered groups (20 mg and 40 mg/ 100 g body weight) for 16 days. SPC reversed the toxic effects of NaF. SPC significantly ameliorated the NaF-induced alterations of the antioxidant system in the uterus by decreasing lipid peroxidation products and by increasing antioxidant activities. SPC significantly counteracted the adverse effects of NaF on serum level of lactate dehydrogenase (LDH) and inflammatory markers Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and nuclear factor kappa-B (NF-κB). Our results also explored that lipid profile was meaningfully altered due to NaF and also focused a diminution of circulating homocysteine (Hcy) and altered lipid profiles along with a diminished quantity of serum B12 and B9. However, both the doses of SPC reverted back serum levels of B12, B9, and Hcy status in similar fashion along with its corrective action on lipid profile. NaF-treated group exhibited a marked degree of reduction in the weights of ovary and uterus with an alteration of normal tissue histology and significant diminution in serum estradiol (ES) levels without fluctuating uterine estradiol receptor-α (ER-α). However, SPC restored the normal tissue histoarchitecture and also increased the functional efficiency and expression of the ER-α receptor by overturning the ES levels in NaF-treated rats. Moreover, both the doses of SPC were effective against NaF-induced alterations, although 40 mg SPC/100 g body weight had better efficacy in ameliorating the NaF-induced adverse effects on the uterus and ovary.

The consequence of NAC on sodium arsenite-induced uterine oxidative stress.

Arsenic consumption through drinking water is a worldwide major health problem. Management of arsenic intoxication with invasive, painful therapy using metal chelators is usually used as a conventional treatment strategy in human. In this present study, we examined the efficacy of oral administration of N-acetyl l-cysteine (NAC) in limiting arsenic-mediated female reproductive disorders and oxidative stress in female Wistar rats. The treatment was continued for 8 days (2 estrus cycles) on rats with sodium arsenite (10 mg/Kg body weight) orally. We examined the electrozymographic imprint of three different enzymatic antioxidants in uterine tissue. Rats fed with sodium arsenite exhibited a significant lessening in the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Uterine DNA breakage, necrosis, ovarian and uterine tissue damage, disruption in steroidogenesis were also found in arsenic treated rats. Co-administration of NAC at different doses (50 mg/kg body weight, 100 mg/kg body weight, respectively) significantly reversed the action of uterine oxidative stress markers like malondialdehyde (MDA), conjugated dienes (CD) and non protein soluble thiol (NPSH); and noticeably improved antioxidant status of the arsenic fed rats. This ultimately resulted in the uterine tissue repairing followed by improvement of ovarian steroidogenesis. However, this effective function of NAC might be crucial for the restoration of arsenic-induced female reproductive organ damage in rats.

Arjunolic Acid Improves the Serum Level of Vitamin B12 and Folate in the Process of the Attenuation of Arsenic Induced Uterine Oxidative Stress.

Continuation of prolonged treatment against arsenicosis with conventional chelating therapy is a global challenge. The present study was intended to evaluate the defensive effect of arjunolic acid against arsenic-induced oxidative stress and female reproductive dysfunction. Wistar strain adult female rats were given sodium arsenite (10 mg/kg body weight) in combination with arjunolic acid (10 mg/kg body weight) orally for two estrous cycles. Electrozymographic analysis explored that arjunolic acid co-treatment counteracted As3+-induced ROS production in uterine tissue by stimulating the activities of endogenous enzymatic antioxidants. Arjunolic acid was able to enhance the protection against mutagenic uterine DNA breakage, necrosis, and ovarian-uterine tissue damages in arsenicated rats by improving the ovarian steroidogenesis. The mechanisms might be coupled with the augmentation of antioxidant defense system, partly through the elimination of arsenic with the involvement of S-adenosyl methionine pool where circulating levels of vitamin B12, folic acid, and homocysteine play critical roles as evidenced from our present investigation.

Electrozymographic evaluation of the attenuation of arsenic induced degradation of hepatic SOD, catalase in an in vitro assay system by pectic polysaccharides of Momordica charantia in combination with curcumin.

Momordica charantia (MC) fruit known as bitter gourd, is of potential nutritional and medicinal value. The objectives of the present in vitro study were to evaluate the efficacy of bioactive pectic polysaccharides (CCPS) of MC along with another well-known bioactive compound curcumin in the abrogation of hepatocellular oxidative stress persuaded by sodium arsenite. Electrozymographic method was developed for the assessment of superoxide dismutase (SOD) and catalase activities of liver tissues maintained under an in vitro system. A significant association of CCPS of MC in combination with curcumin was found in the alleviation of oxidative stress induced by sodium arsenite in liver slice. Generated data pointed out that CCPS of MC and curcumin separately or in combination can offer significant protection against alterations in malondialdehyde (MDA), conjugated diene (CD) and antioxidative defense (SOD, CAT) markers. Furthermore, results of hepatic cell DNA degradation strongly supported that both these co-administrations have efficacy in preventing cellular damage. This is the first information of extracted polysaccharides from MC preventing arsenic induced damage in a liver slice of rat.