The abundant use of lead (Pb; toxic heavy metal) worldwide has increased occupational and ecosystem exposure, with subsequent negative health effects. The flavonoid luteolin (LUT) found in many natural foodstuffs possesses antioxidant and anti-inflammatory properties. Herein, we hypothesized that LUT could mitigate liver damage induced by exposure to lead acetate (PbAc). Male Wistar rats were allocated to four groups: control group received normal saline, LUT-treated group (50 mg/kg, oral, daily), PbAc-treated group (20 mg/kg, i.p., daily), and LUT+PbAc-treated group (received the aforementioned doses via the respective routes of administration); the rats were treated for 7 days. The results revealed that PbAc exposure significantly increased hepatic Pb residue and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin value. Oxidative reactions were observed in the liver tissue following PbAc intoxication, characterized by the depletion and downregulation of antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1), and an increase in oxidants (malondialdehyde and nitric oxide). Additionally, PbAc increased the release and expression of the pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1 beta), inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, PbAc enhanced hepatocyte loss by increasing the expression of pro-apoptotic proteins (Bax and caspase-3) and downregulating the anti-apoptotic protein (Bcl-2). The changes in the aforementioned parameters were further confirmed by noticeable histopathological lesions. LUT supplementation significantly reversed all of the tested parameters in comparison with the PbAc-exposed group. In conclusion, our findings describe the potential mechanisms involved in the alleviation of PbAc-induced liver injury by luteolin via its potent anti-inflammatory, antioxidant, and anti-apoptotic properties.

Heavy metal exposure, in lead (Pb) particularly, is associated with severe neuronal impairment though oxidative stress mediated by reactive oxygen species, and antioxidants may be used to abolish these adverse effects. This study investigated the potential neuroprotective role of coenzyme Q10 (CoQ₁₀) against lead acetate (PbAc)-induced neurotoxicity. Twenty-eight male Wistar albino rats were divided into four equal groups (n = 7) and treated as follows: the control group was injected with physiological saline (0.9% NaCl); the CoQ₁₀ group was injected with CoQ₁₀ (10 mg/kg); PbAc group was injected with PbAc (20 mg/kg); PbAc + CoQ₁₀ group was injected first with PbAc, and after 1 h with CoQ₁₀. All groups were injected intraperitoneally for seven days. PbAc significantly increased cortical lipid peroxidation, nitrate/nitrite levels, and inducible nitric oxide synthase expression, and decreased glutathione content, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase activity and mRNA expression, as well as nuclear factor erythroid 2–related factor 2 (Nrf2) and homoxygenase-1 (HO-1) expression. PbAc also promoted the secretion of interleukin-1ß and tumor necrosis factor-α, inhibited interleukin-10 production, triggered the activation of pro-apoptotic proteins, and suppressed anti-apoptotic proteins. Additionally, PbAc increased the cortical levels of serotonin, dopamine, norepinephrine, GABA, and glutamate, and decreased the level of ATP. However, treatment with CoQ₁₀ rescued cortical neurons from PbAc-induced neurotoxicity by restoring the balance between oxidants and antioxidants, activating the Nrf2/HO-1 pathway, suppressing inflammation, inhibiting the apoptotic cascade, and modulating cortical neurotransmission and energy metabolism. Altogether, our findings indicate that CoQ₁₀ has beneficial effects against PbAc-induced neuronal damage through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activities.

Background: Pomegranate fruit has been extensively used as a natural medicine in many cultures. The present study was aimed at evaluating the protective effects of pomegranate (Punica granatum) juice against carbon tetrachloride (CCl₄)-induced oxidative stress and testes injury in adult Wistar rats. Methods: Twenty eight Wistar albino male rats were divided equally into 4 groups for the assessment of protective potential of pomegranate juice. Rats of group I (control) received only vehicles and had free access to food and water. Rats of groups II and IV were treated with CCl₄ (2 ml/kg bwt) via the intraperitoneal route once a week for ten weeks. The pomegranate juice was supplemented via drinking water 2 weeks before and concurrent with CCl₄ treatment to group IV. Group III was supplemented with pomegranate juice for twelve weeks. The protective effects of pomegranate on serum sex hormones, oxidative markers, activities of antioxidant enzymes and histopathology of testes were determined in CCl₄-induced reproductive toxicity in rats. Results: Pomegranate juice showed significant elevation in testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) those depleted by the injection of CCl₄. Activity levels of endogenous testesticular antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and glutathione (GSH) contents were increased while lipid peroxidation (LPO) and nitric oxide (NO) were decreased with pomegranate juice. Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl₄ injections were restored with the treatment of pomegranate juice. Conclusion: The results clearly demonstrated that pomegranate juice augments the antioxidant defense mechanism against carbon tetrachloride-induced reproductive toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.

Cadmium is a deleterious environmental pollutant that threats both animals and human health. Oxidative stress and elevated levels of reactive oxygen species (ROS) have recently been reported to be the main cause of cellular damage as a result of cadmium exposure. We investigate, here, the protective effect of strawberry crude extracts on cadmium-induced oxidative damage of testes in rats. Four groups (n = 8) of 32 adult male Wistar rats weighing 160–180 g were used. The control group received 0.9% saline solution all over the experimental period (5 days). Group 2 was intraperitoneally injected with 6.5 mg/kg CdCl₂. Group 3 was provided only with an oral administration of strawberry methanolic extract (SME) at a dose of 250 mg/kg. Group 4 was treated with SME before cadmium injection with the same mentioned doses. It was shown that cadmium exposure results in a significant decrease in both relative testicular weight and serum testosterone level. Analyzing the oxidative damaging effect of cadmium on the testicular tissue revealed the induction of oxidative stress markers represented in the elevated level of lipid peroxidation (LPO), nitric oxide (NO), and a decrease in the reduced glutathione (GSH) content. Considering cadmium toxicity, the level of the antioxidant enzyme activities including catalase (CAT), superoxide dismutase (SOD2), glutathione peroxidase (GPx1), and glutathione reductase (GR) were markedly decreased. Moreover, gene expression analysis indicated significant upregulation of the pro-apoptotic proteins, bcl-2-associated-X-protein (BAX), and tumor necrosis factor-α (TNFA) in response to cadmium intoxication, while significant downregulation of the anti-apoptotic, B-cell lymphoma 2 (BCL2) gene was detected. Immunohistochemistry of the testicular tissue possessed positive immunostaining for the increased level of TNF-α, but decreased number of proliferating cell nuclear antigen (PCNA) stained cells. Administration of SME debilitated the deleterious effect of cadmium via reduction of both LPO and NO levels followed by a significant enhancement in the gene expression level of CAT, SOD2, GPX1, GR, nuclear factor-erythroid 2-related factor 2 (NFE2L2), heme oxygenase-1 (HMOX1), Bcl-2, and PCNA. In addition, the SME treated group revealed a significant increase in the level of testosterone and GSH accompanied by a marked decrease in the gene expression level of Bax and TNF-α. In terms of the summarized results, the SME of Fragaria ananassa has a protective effect against cadmium-induced oxidative damage of testes.

The kidney is among the metabolic organs most susceptible to injury, particularly following exposure to xenobiotics and heavy metals. We aimed to explore the potential protective impacts of coenzyme Q10 (CoQ10) on lead acetate (PbAc)-induced nephrotoxicity in rats. Four experimental groups (n = 7) were applied as follows: control group, CoQ10 alone (10 mg/kg), PbAc alone (20 mg/kg), and PbAc with CoQ10. Exposure to PbAc led to the accumulation of Pb in the kidney and increased urea and creatinine serum levels. The deposition of Pb coupled with the elevation of malondialdehyde and nitrate/nitrite levels along with the upregulation of inducible nitric oxide synthase. Additionally, upon PbAc poisoning, glutathione content and the antioxidant enzymes were depleted along with the downregulation of Nrf2 and HO-1 expression. Moreover, PbAc injection increased the protein and mRNA levels of pro-inflammatory cytokines namely, tumor necrosis factor-alpha and interleukin-1 beta, while decreased the levels of interleukin-10, an anti-inflammatory cytokine, in the kidney. Furthermore, exposure to PbAc correlated with increased levels of pro-apoptotic markers, Bax and caspase-3, and reduced levels of the anti-apoptotic marker Bcl-2. The administration of CoQ10 alleviated the molecular, biochemical and histological changes following PbAc intoxication. Thus, CoQ10 reduces the deleterious cellular side effects of PbAc exposure due to its antioxidant, anti-inflammatory and anti-apoptotic effects.

Leishmaniasis is one of the most significant vector-borne syndromes of individuals. This parasitic infection can be affected by many species of Leishmania, most of which are zoonotic. Natural products have made and are continuing to make important contributions to the search for new antileishmanial agents. The use of plants in the production assembly of silver nanoparticles has drawn attention because of its rapid, eco-friendly, non-pathogenic, economical protocol and provides a single step technique for the biosynthetic process. Hence, we aimed to biosynthesize silver nanoparticles (Ag-NPs) using Moringa oleifera leaf extract and investigated the antileishmanial activity of these nanoparticles in a murine model of Leishmania major infection. A total of 50 mice were used and divided into five groups—healthy control, infected, infected mice treated with pentostam, infected mice treated with Ag-NPs and infected mice pretreated with Ag-NPs. In the present study, the leaf extract of the plant species Moringa oleifera was found to be a good source for the synthesis of silver nanoparticles, their formation being confirmed by color change and stability in solution. In the present murine model of Leishmania major infection, we found that oral treatment with silver nanoparticles biosynthesized using Moringa oleifera extract resulted in a significant reduction in the average size of leishmaniasis cutaneous lesions compared with untreated mice. Furthermore, the clinical efficacy of Moringa oleifera extract was associated with enhanced antioxidant enzyme activities. In conclusion, treatment with silver nanoparticles biosynthesized using Moringa oleifera extract has higher and faster clinical efficacy than standard pentavalent antimonial treatment, probably by boosting the endogenous antioxidant activity.