THE PECULIARITIES OF MORPOLOGICAL CHANGES OF RATS' OVARY AND BIOCHEMICAL STATE UNDER THE DAMAGE WITH DIFFERENT DOSES OF LEAD ACETATE.

OBJECTIVE: The aim of the study was to study the effect of low and high doses of lead acetate on biochemical parameters and morphological status of rat ovaries in the experiment. PATIENTS AND METHODS: Materials and methods: The study was performed on 36 nonlinear female rats weighing 180-210 g, aged 4 months, divided into 3 experimental groups: I - control (C), II - rats, which were given 30 days to drink a solution of lead acetate with at the rate of 0,05 mg / kg of animal weight, group III - rats, which were given for 30 days to drink a solution of lead acetate at the rate of 60 mg/kg of animal weight. Biochemical research methods were included determination of diene conjugate concentration in animals' blood, concentration of TBA-active products, study of oxidative modification of proteins in blood plasma, determination of superoxide dismutase and catalase activities. Endogenous intoxication was assessed by the definition of medium-mass molecules, the content was expressed in units of extinction. The material for light microscopy investigation from the ovary was performed according to the generally accepted method. RESULTS: Results: Lead acetate causes activation of peroxidation of lipids and proteins in the body of female rats, which is directly dependent on the dose of lead. In response to the activation of free radical oxidation there are changes in the antioxidant system, which depend on the dose of lead acetate: at a dose of 0.05 mg / kg superoxide dismutase and catalase activity increase, at a dose of 60 mg / kg superoxide dismutase and catalase activity. Small doses of lead do not cause endogenous intoxication. Lead acetate causes the development of endogenous intoxication in animals only in large doses: increases the formation of toxic compounds, cell apoptosis, decreased excretory function of the kidneys, which is associated with multiorgan disorders. As a result of the action of lead acetate, morphological changes of the ovaries were observed, which increased with increasing dose of lead acetate. There was a dose-dependent decrease in massometric parameters, the number of follicles and changes in the thickness of the surface structures of the ovary, which is more pronounced at 60 mg/kg. CONCLUSION: Conclusions: Under the influence of small and large doses of lead acetate on biochemical changes in blood and morphological changes in the ovaries in male rats the oxidative stress is developed. Under the influence of small doses, the changes are adaptive, and under the influence of large doses - damaging.

Wild Garlic Allium triquetrum L. Alleviates Lead Acetate-Induced Testicular Injuries in Rats.

The current study investigates the potential alleviating activity of bulbs (B) and leaves (L) of Allium triquetrum aqueous extract (ATE) on repro-toxicity induced by lead acetate (Pb) in male Wistar rats administrated orally for 3 consecutive weeks. Eighteen groups of rats were divided into the control, Pb (500 mg/kg body weight/day), positive controls of B and L (2 g, 3 g, 4 g, 6 g/kg body weight/day), in addition to four mixtures of each of Pb-B (Pb-B1, Pb-B2, Pb-B3, Pb-B4) and Pb-L (Pb-L1, Pb-L2, Pb-L3, Pb-L4). The two extracts were subjected to phytochemical screening and HPLC analysis. Sperm characteristics were evaluated by CASA system, as well as the serum testosterone, testicular and epididymal levels of glutathione (GSH), glutathione peroxidase (GPx), and malondialdehyde (MDA). The phytochemical screening proved that bulbs' and leaves' extracts were rich in various compounds and the HPLC showed that leaves contain more tannins. Results revealed a significant decrease in the testicular and in the epididymal weights, sperm concentration, motility, testosterone, velocity, vitality, round cells, GSH, and GPx levels in the Pb-intoxicated rats compared to the control, with the exception of MDA concentration that was significantly increased. However, the co-administration of garlic extracts (Pb-B and Pb-L) exhibited a significant increase in all mentioned markers, except for the MDA level which was reduced. Likewise, Pb caused histological injuries in the testicular seminiferous of rats, while the co-administration of wild garlic has reduced such effect, especially in the higher doses. Both extracts of Pb-B and Pb-L have attenuated Pb toxicity in a dose-dependent manner. In conclusion, aqueous extracts of A. triquetrum have the potential to reduce Pb testicular injuries by boosting sperm characteristics and ameliorating oxidative stress markers.

Study on the Efficacy and Mechanism of Lycium barbarum Polysaccharide against Lead-Induced Renal Injury in Mice.

Lead is one of the most common heavy metal pollutants in the environment. Prolonged exposure to lead will induce oxidative stress, inflammation, and apoptosis in the kidneys, which in turn causes kidney injury. Lycium barbarum polysaccharide (LBP) is well known for its numerous pharmacological properties. This study aims to explore the efficacy and mechanism of LBP against lead-induced kidney damage in mice. Symptoms of renal injury were induced in mice by using 25 mg/kg lead acetate (PbAc2), and different doses of LBP (200, 400, and 600 mg/kg BW) were orally administrated to PbAc2-treated mice for five weeks. The results of the pharmacodynamics experiment showed that the renal pathological damages, serum creatinine (Cre), blood urea nitrogen (BUN), and kidney index of PbAc2-treated mice could be significantly alleviated by treatment with LBP. Further, LBP treatment significantly increased the weight and feed intake of PbAc2-treated mice. The dose effect results indicated that a medium dose of LBP was superior to high and low doses. The results of mechanistic experiments showed that LBP could attenuate oxidative stress, inflammation, and apoptosis in the kidneys of mice with lead toxicity by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

A toxicological evaluation of lithium orotate.

Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5-67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption.

The protective role of Coenzyme Q10 in metallothionein-3 expression in liver and kidney upon rats' exposure to lead acetate.

Metallothionein-3 (MT3) is an antioxidant protein that alters after exposure to heavy metals. In this study, we investigated the hepatic and renal expression of MT3 gene following exposure to lead acetate (PbAc) alone and PbAc plus CoQ10 as an adjuvant antioxidant. Twenty-four rats were allocated into three groups, including control, PbAc (free access to drinking water contaminated with PbAc at 1 g/100 ml), and PbAc plus CoQ10 (10 mg/kg/day Oral). After 28 consecutive days of treatment, the mRNA expression of MT3 and Cyt-c genes and MT3 protein levels were assessed using real-time PCR and immunosorbent assay. The serum lipid profile was also monitored in the three groups. PbAc exposure significantly reduced the hepatic and renal MT3 mRNA and protein expression compared to the control group. This reduction was significantly increased with addition of CoQ10 to levels near those of the control group. The hepatic and renal expression of Cyt-c mRNA increased after treatment with PbAc, while such effect was reversed after addition of CoQ10. Alteration in lipid profile including increased cholesterol and low-density lipoprotein levels were observed after PbAc exposure which were counteracted by CoQ10. Our results confirm the cytotoxic effects of acute lead exposure manifested as changes in the serum lipid profile and cellular levels of Cyt-c mRNA. These cytotoxic effects may have been caused by decreased MT3 gene expression and be reduced by the protective role of CoQ10.

Ameliorative effect of L-carnitine on chronic lead-induced reproductive toxicity in male rats.

Lead toxicity is one of the causative agents of male infertility that raised concern from environmental contamination worldwide. L-carnitine, a biologically active amino acid, present in high concentration in the reproductive organs such as the epididymis, is involved in sperm maturation. The possible protective effect of L-carnitine in experimentally lead-induced male reproductive toxicity in rats was evaluated in this study. Thirty adult male Wistar rats were divided into three groups. Group 1: the negative control group was treated with normal saline; Group 2: exposed to 50 mg/kg lead acetate (2% solution in saline); and Group 3: treated with lead acetate 50 mg/kg (2% solution in saline) + L-carnitine 100 mg/kg. At the end of the experimental period, body and testicular weights were determined, blood samples were withdrawn for hormonal assays of FSH, LH and testosterone. Sperm parameters as sperm count, morphology, viability and motility were measured. Testicular tissue homogenates were prepared for enzymatic assays and for measuring oxidative stress parameters. Lead significantly increased both oxidative stress and the concentration of lactate dehydrogenase-C in the testicular tissues with a decrease in sperm count, motility and viability. Lead acetate treatment, induced alteration in sperms with normal morphology together with reductions in the serum FSH, LH, testosterone, body and testicular weights. The concentration of 17ß-hydroxysteroid dehydrogenase was significantly reduced. Co-administration of L-carnitine significantly reduced testicular oxidative stress, improved sperm parameters, elevated serum FSH, LH and testosterone with an insignificant reduction in the testicular weight. The concentrations of 17ß-hydroxysteroid dehydrogenase and lactate dehydrogenase-C were significantly improved by L-carnitine. The overall results indicate that L-carnitine is expected to improve the lead acetate-induced male reproductive toxicity.

Gallium maltolate has in vitro antiviral activity against SARS-CoV-2 and is a potential treatment for COVID-19.

BACKGROUND: Gallium has demonstrated strong anti-inflammatory activity in numerous animal studies, and has also demonstrated direct antiviral activity against the influenza A H1N1 virus and the human immunodeficiency virus (HIV). Gallium maltolate (GaM), a small metal-organic coordination complex, has been tested in several Phase 1 clinical trials, in which no dose-limiting or other serious toxicity was reported, even at high daily oral doses for several months at a time. For these reasons, GaM may be considered a potential candidate to treat coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus and can result in severe, sometimes lethal, inflammatory reactions. In this study, we assessed the ability of GaM to inhibit the replication of SARS-CoV-2 in a culture of Vero E6 cells. METHODS: The efficacy of GaM in inhibiting the replication of SARS-CoV-2 was determined in a screening assay using cultured Vero E6 cells. The cytotoxicity of GaM in uninfected cells was determined using the Cell Counting Kit-8 (CCK-8) colorimetric assay. RESULTS: The results showed that GaM inhibits viral replication in a dose-dependent manner, with the concentration that inhibits replication by 50% (EC50) being about 14 µM. No cytotoxicity was observed at concentrations up to at least 200 µM. CONCLUSION: The in vitro activity of GaM against SARS-CoV-2, together with GaM's known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.

Alleviation of lead acetate-induced nephrotoxicity by Moringa oleifera extract in rats: highlighting the antioxidant, anti-inflammatory, and anti-apoptotic activities.

Lead (Pb) is an environmental toxicant; its consumption can induce renal deficits. In this study, we explored the possible protective efficiency of Moringa oleifera extract (MOE) against lead acetate (PbAc)-mediated reprotoxicity. Four experimental groups of seven rats each were used: control, PbAc, MOE, and MOE+PbAc groups. All groups were given their respective treatment for 4 weeks. PbAc impaired the oxidative/antioxidative balance in the renal tissue, as shown by the decreased antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase) and increased oxidants (lipid peroxidation and nitric oxide). Additionally, PbAc enhanced the progression of kidney inflammation by increasing tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B associated with upregulation of inducible nitric oxide synthase. Moreover, a dysregulation in the apoptotic-regulating proteins (Bax, caspase-3, and Bcl2) were recorded upon PbAc exposure. Remarkably, MOE oral administration restored redox homeostasis, suppressed the inflammatory and apoptotic responses in the kidney tissue. Our findings point out that MOE could be used as an alternative remedy to overcome the adverse effects of Pb exposure, which may be due to its potent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats.

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n = 7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v : v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

Ameliorative effect of curcumin on lead-induced hematological and hepatorenal toxicity in a rat model.

INTRODUCTION: Lead (Pb) is a ubiquitous toxic heavy metal that inflicts numerous clinical consequences on humans. Curcumin is the principal component of turmeric, which is reported to have antioxidative properties. This study aimed at evaluating the ameliorative effects of curcumin on Pb-induced hepatorenal toxicity in a rat model. METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned into five groups with 12 rats in the control (normal saline) and six rats each for the lead-treated group (LTG) (50 mg/kg lead acetate [Pb acetate] for 4 weeks), recovery group (50 mg/kg Pb acetate for 4 weeks and left with no treatment for another 4 weeks), treatment group 1 (Cur100) (50 mg/kg Pb acetate for 4 weeks, followed by 100 mg/kg curcumin for 4 weeks), and treatment group 2 (Cur200) (50 mg/kg Pb acetate for 4 weeks, followed by 200 mg/kg curcumin for 4 weeks). All the experimental groups received oral treatments via orogastric-tube on alternate days. Pb concentration in the liver and kidney of the rats were evaluated using inductive-coupled plasma mass spectrometry techniques. RESULTS: Pb-administered rats revealed significant alteration in oxidative status and increased Pb concentration in their liver and kidney with obvious reduction of hemogram and increased in leukogram as well as aberration in histological architecture of the liver and kidney. However, treatment with curcumin reduces the tissue Pb concentrations and ameliorates the above mention alterations. CONCLUSIONS: The results in this study suggested that curcumin attenuates Pb-induced hepatorenal toxicity via chelating activity and inhibition of oxidative stress.

Role of some natural anti-oxidants in the down regulation of Kim, VCAM1, Cystatin C protein expression in lead acetate-induced acute kidney injury.

BACKGROUND: Lead is a dangerous systemic toxicant and can provoke life-threatening renal injury. The plan of this study was to evaluate the potential impact of curcumin (CRMN) and L-ascorbic acid (L-ascb) alone or together to counteract lead acetate (Pb-acetate)-induced renal damage in rats and to find out the underlying mechanisms of action of these nutraceuticals. METHODS: Pb-acetate (100 mg/kg/day, i.p.) was injected in male rats along with L-ascb (250 mg/kg/day) and/or CRMN (200 mg/kg/day) orally for 7 days. RESULTS: Pb-acetate administration increased serum urea, creatinine and uric acid. Renal tissue showed a marked depletion in reduced glutathione level and superoxide dismutase activity and elevation in nitric oxide and malondialdehyde levels. Serum C-reactive protein and IL-1ß levels were elevated. Up-regulation of the expression of kidney injury molecule, vascular adhesion molecule-1 and Cystatin C were noticed after Pb-acetate administration. DNA fragmentation was also increased in renal tissues. Histopathological examination revealed a destructed partial layer of Bowman's capsule, proximal and distal convoluted tubules. Treatment with the aforementioned antioxidants ameliorated most of the altered measured biomarker levels. CONCLUSION: Interestingly, the combination of L-ascb and CRMN showed the superlative protective effect against Pb-acetate-induced nephrotoxicity.

Protective effects of spirulina against hemato-biochemical alterations, nephrotoxicity, and DNA damage upon lead exposition.

The current study was aimed at exploring the protective efficacy of spirulina against the hemato-biochemical alterations and nephrotoxicity induced by lead (Pb). Female rats aged 12 weeks were treated for 4 weeks with Pb (0.344 g kg-1 bw) associated or not with spirulina (5.3 g kg-1 bw). Renal damage induced by Pb was related to a severe anemia, increases of oxidative stress-related parameters (thiobarbituric acid reactive substances (TBARS) (+29%), protein carbonyl (PCO) (+66.3%), and advanced oxidation protein product (AOPP) (+110%)), plasma lactate dehydrogenase (LDH) (+80%), creatinine and urea levels in plasma, and uric acid concentration in urine, as well as genotoxic changes (+89.3% and +60% for DNA and mRNA levels, respectively). Conversely, LDH and antioxidant enzyme activities in kidney were decreased, as well as the levels of plasma uric acid, and urinary creatinine and urea levels. Spirulina-supplemented rats exhibited normal peripheral blood and renal parameters and renal histology. It can be suggested that Arthrospira platensis alleviates damages induced by Pb, thanks to its high phenolic content and antioxidant capacity.

Late-life Cardiac Injury in Rats following Early Life Exposure to Lead: Reversal Effect of Nutrient Metal Mixture.

Early-life exposure to lead (Pb) can lead to health effects in later life. The neurotoxic effects of Pb have been well documented but its effects on the heart are poorly elucidated. We examined the late life cardiac impairments resulting from developmental exposure to Pb. Further, we investigated the protective effect of the nutrient metal mixture containing calcium (Ca), zinc (Zn) and iron (Fe) against Pb-induced long-term effects on cardiac functions.Male albino rats were lactationally exposed to 0.2% Pb-acetate or 0.2% Pb-acetate together nutrient metal mixture as 0.02% in drinking water of the mother from PND 1 to PND 21. The results showed increased levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDLs) and lactate dehydrogenase (LDH) activity at postnatal day (PND) 28 [young], 4 months [adult] and 18 months [old] age group rats. Most notably, exposure to Pb decreased the activities of mitochondrial superoxide dismutase (SOD), thioredoxin reductase (TrxR), aconitase (Acon), isocitrate dehydrogenase (ICDH), xanthine oxidase (XO) and total antioxidant status while the MDA levels increased in all selected age groups of rats. The histological findings showed an age-dependent response to Pb exposure evidenced by extensive degeneration and necrosis in cardiac muscle, disruption in muscle connectivity, hemorrhage, and mononuclear cell infiltration. Co-administration of nutrient metal mixture reversed the Pb-induced cardiac impairments as reflected in the recovery of the chosen sensitive markers of oxidative stress, reduced Pb levels and cardiac tissue changes. In conclusion, the data demonstrate that early-life exposure to Pb continuously influence the cardiac mitochondrial functions from early life to older age and further suggesting that adequate intake of nutrient metals may be potential therapeutic treatment for Pb intoxication.

Ferulago angulata extract ameliorates epididymal sperm toxicity in mice induced by lead and diazinon.

BACKGROUND: The potential toxicity that results from environmental xenobiotics is not completely known. Increasing levels of heavy metals and the use of organophosphate pesticides (OPs) and their co-existence in the environment could be associated with an increasing incidence of male reproductive system disorders in humans and animals. Ferulago angulata is a dietary source of phenolic compounds with reported health benefits. OBJECTIVE: This study was conducted to investigate whether an extract of Ferulago angulata could protect adult male NMRI mice against reproductive toxicity induced by lead acetate (PbAc), diazinon (DZN), or PbAc + DZN. MATERIALS AND METHODS: Adult male NMRI mice were exposed to either 0.5% PbAc in drinking water, DZN (3 mg/kg/day, intraperitoneal [i.p.] injection), or PbAc + DZN in the presence or absence of 400 mg/kg/day Ferulago angulata hydroalcoholic extract (FAE) that was administered via gavage for 6 weeks. RESULTS: Chronic exposure to PbAc, DZN, and PbAc + DZN decreased sperm quality, sperm chromatin maturity and integrity, increased oxidative stress and lipid peroxidation, and could reduce male fertility indices. Co-administration of FAE could reduce these negative effects. CONCLUSION: The Ferulago angulata extract should be considered as a useful natural extract for the treatment of male infertility, especially in males exposed to conditions which induce reproductive toxicity.

Uranium Effect on Osteocytic Cells In Vitro.

Once absorbed in the body, natural uranium [U(VI)], a radionucleotide naturally present in the environment, is targeted to the skeleton which is the long-term storage organ. We and others have reported the U(VI) negative effects on osteoblasts (OB) and osteoclasts (OC), the main two cell types involved in bone remodeling. In the present work, we addressed the U(VI) effect on osteocytes (OST), the longest living bone cell type and the more numerous (> 90%). These cells, which are embedded in bone matrix and thus are the more prone to U(VI) long-term exposure, are now considered as the chief orchestrators of the bone remodeling process. Our results show that the cytotoxicity index of OST is close to 730 µM, which is about twice the one reported for OB and OC. However, despite this resistance potential, we observed that chronic U(VI) exposure as low as 5 µM led to a drastic decrease of the OST mineralization function. Gene expression analysis showed that this impairment could potentially be linked to an altered differentiation process of these cells. We also observed that U(VI) was able to trigger autophagy, a highly conserved survival mechanism. Extended X-ray absorption fine structure analysis at the U LIII edge of OST cells exposed to U(VI) unambiguously shows the formation of an uranyl phosphate phase in which the uranyl local structure is similar to the one present in Autunite. Thus, our results demonstrate for the first time that OST mineralization function can be affected by U(VI) exposure as low as 5 µM, suggesting that prolonged exposure could alter the central role of these cells in the bone environment.

Chirality-Selected Chemical Modulation of Amyloid Aggregation.

Due to the composed α-helical/ß-strand structures, ß-amyloid peptide (Aß) is sensitive to chiral environments. The orientation and chirality of the Aß strand strongly influence its aggregation. Aß-formed fibrils have a cascade of chirality. Therefore, for selectively targeting amyloid aggregates, chirality preference can be one key issue. Inspired by the natural stereoselectivity and the ß-sheet structure, herein, we synthesized a series of d- and l-amino acid-modified polyoxometalate (POM) derivatives, including positively charged amino acids (d-His and l-His) and negatively charged (d-Glu and l-Glu) and hydrophobic amino acids (d-Leu, l-Leu, d-Phe, and l-Phe), to modulate Aß aggregation. Intriguingly, Phe-modified POMs showed a stronger inhibition effect than other amino acid-modified POMs, as evidenced by multiple biophysical and spectral assays, including fluorescence, circular dichroism, NMR, molecular dynamic simulations, and isothermal titration calorimetry. More importantly, d-Phe-modified POM had an 8-fold stronger inhibition effect than l-Phe-modified POM, indicating high enantioselectivity. Furthermore, in vivo studies demonstrated that the chiral POM derivatives crossed the blood-brain barrier, extended the life span of AD transgenic Caenorhabditis elegans CL2006 strain, and had low cytotoxicity, even at a high dosage.

Bacopa phospholipid complex retrieves aluminum maltolate complex-induced oxidative stress and apoptotic alterations in the brain regions of albino rat.

Highly bioavailable plant phospholipid complex that can reverse aluminum maltolate (AlM)-induced toxicity is not yet reported. Hence, the present study was planned to investigate the impact of oxidative stress and apoptotic changes provoked by Al and ameliorative role of Bacopa phospholipid complex (BPC) in albino rats. The levels of antioxidant enzymes such as superoxide dismutase (SOD), catalase activity (CAT), glutathione peroxidase (GPx), and thiobarbituric acid-reactive substance (TBA-RS) were measured and immunohistochemistry analysis of apoptotic markers, Bax and Bcl-2, was done from the four brain regions such as the hippocampus, cerebral cortex, cerebellum, and medulla oblongata. The levels of antioxidant enzymes and apoptotic markers that were decreased on AlM induction showed a significant increase in their levels, almost as observed in the control, when treated with BPC and Bm. Our results indicate that both BPC and Bm showed a therapeutic effect against AlM toxicity; however, it was found that the therapeutic potential of BPC was more pronounced than Bm against AlM-induced neurotoxicity.

Effects of Concurrently Administered Aqueous Extract of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), and Lead Acetate in Rats.

Ganoderma lucidum is a hard, bitter mushroom with many ethnomedicinal uses, including conditions similar to lead (Pb) toxicity. The aim of this study was to evaluate the protective effects of a G. lucidum aqueous extract (GL) when concurrently administered with Pb. Adult Wistar rats were administered oral doses of Pb (100 mg/kg) daily for 25 consecutive days. Of the Pb-treated rats, 3 groups received 100, 200, or 400 mg/kg/day GL, respectively; one group was given only 50 mg/kg/day 2,3-dimercaptosuccinic acid (DMSA); and another group was given 400 mg/kg/day GL and 50 mg/kg/day DMSA. Body weight, Pb levels in organs, enzyme and lipid levels in serum, and antioxidant capability were evaluated. Body weights were not significantly altered by GL. All doses of GL significantly reduced the amount of Pb in the liver (P < 0.01) and kidneys (P < 0.05), but not in the spleen. Doses of GL significantly reduced (P < 0.05) amounts of low-density lipoprotein, but not high-density lipoprotein or triglycerides, in serum. Pb-induced increases in amounts of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly (P < 0.01) attenuated by GL. Also, a Pb-induced reduction in the amount of superoxide dismutase was significantly (P < 0.05) reversed, but the nitric oxide level was not significantly elevated. An increased malondialdehyde level, which had been induced by Pb, was significantly (P < 0.01) reversed. In conclusion, GL protects against some of the deleterious effects of Pb ingestion, possibly through antioxidant and other mechanisms. DMSA did not enhance the beneficial effects of GL.

Countering the effects of lead as an environmental toxicant on the microanatomy of female reproductive system of adult wistar rats using aqueous extract of Ficus vogelii.

BACKGROUND: Lead without nutritional value is a widely studied occupational and environmental toxicant. Leads' toxic effects on female reproduction are decreased fertility, inability to sustain pregnancy and reduced pregnancy. OBJECTIVE: This study aimed at examining the effect of oral administration of lead acetate (1.5 mg/kg) on the histology of female albino Wistar rats' ovary and Uterus and the extracts' protective role against toxicity. METHODS: The experiment took 28 days involving 25 female Wistar rats divided into 5 groups A, B, C, D and E. A is an untreated group that received normal saline, D lead acetate group that received lead acetate solution, E received aqueous extract, B and C low and high dose of aqueous extract respectively and lead acetate solution. RESULTS: The positive control group showed a significant increase in SOD at P ≤ 0.01 compared to the negative control. Group E showed significant decrease ovarian SOD. The organs weights were significantly reduced in group D. The changes seen in the organs include oedema, necrosis, optical empty spaces, denudations and fatty changes. Administrating the extract protected the organs against the lead acetate. These alterations are shown to cause infertility in female rats. CONCLUSION: The results suggested that the extract has protective role against lead reproductive toxicity.

Carnosine and Histidine Supplementation Blunt Lead-Induced Reproductive Toxicity through Antioxidative and Mitochondria-Dependent Mechanisms.

Lead (Pb)-induced reproductive toxicity is a well-characterized adverse effect associated with this heavy metal. It has been found that Pb exposure is associated with altered spermatogenesis, increased testicular degeneration, and pathological sperm alterations. On the other hand, it has been reported that Pb-induced reproductive toxicity is associated with increased reactive oxygen species (ROS) formation and diminished antioxidant capacity in the reproductive system. Hence, administration of antioxidants as protective agents might be of value against Pb-induced reproductive toxicity. This study was designed to investigate whether carnosine (CAR) and histidine (HIS) supplementation would mitigate the Pb-induced reproductive toxicity in male rats. Animals received Pb (20 mg/kg/day, oral, 14 consecutive days) alone or in combination with CAR (250 and 500 mg/kg/day, oral, 14 consecutive days) or HIS (250 and 500 mg/kg/day, oral, 14 consecutive days). Pb toxicity was evident in the reproductive system by a significant increase in tissue markers of oxidative stress along with severe histopathological changes, seminal tubule damage, tubular desquamation, low spermatogenesis index, poor sperm parameters, and impaired sperm mitochondrial function. It was found that CAR and HIS supplementation blunted the Pb-induced oxidative stress and mitochondrial dysfunction in the rat reproductive system. Thereby, antioxidative and mitochondria-protective properties serve as primary mechanisms for CAR and HIS against Pb-induced reproductive toxicity.