Silica Nanoparticles from Melon Seed Husk Abrogated Binary Metal(loid) Mediated Cerebellar Dysfunction by Attenuation of Oxido-inflammatory Response and Upregulation of Neurotrophic Factors in Male Albino Rats.

Silica nanoparticles (SiNPs) have been touted for their role in the management of non-communicable diseases. Their neuroprotective benefits against heavy metal-induced neurotoxicity remain largely unexplored. This is a comparative evaluation of the oxido-inflammatory and neurotrophic effects of Ni, Al, and Ni/Al mixture on the cerebellum of male albino rats with or without treatment with SiNPs generated from melon seed husk. The study complied with the ARRIVE guidelines for reporting in vivo experiments. A total of 91, 7-9 week-old weight-matched male Sprague rats (to avoid sex bias) were randomly divided into 13 different dosing groups where Group 1 served as the control. Other groups received 0.2 mg/kg Ni, 1 mg/kg Al, and 0.2 mg/kg Ni + 1 mg/kg Al mixture with or without different doses of SiNP for 90 days. Rotarod performance was carried out. Oxidative stress markers, Ni, Al, Ca, Fe, Mg, neurotrophic factors, amyloid beta (Aß-42), cyclooxygenase-2 (COX-2), and acetylcholinesterase (AChE) were determined in the cerebellum. SiNPs from melon seed husk caused a significant decrease in Aß-42 level and activities of AChE and COX-2 and a significant increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mediated by Ni, Al, and Ni/Al mixture exposure in rats. Neurotoxicity of the Ni/Al mixture is via heightened neuronal lipoperoxidative damage, decreased Mg, and increased Fe, and co-administration of SiNPs from melon seed husk with the Ni/Al mixture attenuated some of these biochemical changes in the cerebellum.

Selenium and zinc alleviate hepatotoxicity induced by heavy metal mixture (cadmium, mercury, lead and arsenic) via attenuation of inflammo-oxidant pathways.

Heavy metals (HM) are believed to be injurious to humans. Man is exposed to them on daily basis unknowingly, with no acceptable protocol to manage its deleterious effects. These metals occur as mixture of chemicals with varying concentrations in our atmosphere. There are growing calls for the use of essential metals in mitigating the injurious effects induced by heavy metals exposure to man; therefore, the aim of this study was to evaluate the protective effects of essential metals (Zinc and Selenium) in a mixture of heavy metal toxicity. In this study, except for negative controls, all other groups were treated with lead (PbCl2 , 20 mg kg-1 ); cadmium (CdCl2 , 1.61 mg kg-1 ); mercury (HgCl2 , 0.40 mg kg-1 ), and arsenic (NaAsO3, 10 mg kg-1 ) that were formed in distilled water. Pb, Cd, As, and Hg were administered as mixtures to 35, 6 weeks old rats weighing between 80 to 100 g for 60 days. Group I served as normal control without treatment, group II positive control received HM mixture, while groups III to V received HMM with Zn, Se, and Zn + Se respectively. Animal and liver weights, HM accumulation in the liver, food intake (FI), water intake (WI), liver function test, malondialdehyde (MDA), and inflammatory/transcription factor/apoptosis markers were checked. Also, antioxidant enzymes, and histological studies were carried out. Metal mixture accumulated in the liver and caused toxicities which were ameliorated by Zn and Se administration. HM caused significant decrease in FI, WI and distorted the level of liver enzymes, lipid peroxidation, inflammatory markers, antioxidants and architecture of the liver. Co administration with Zn or Se or both reversed the distortions. This study lays credence to the evolving research on the public health implications of low dose metal mixtures and the possible ameliorative properties of Zn and Se.

Selenium and zinc protect against heavy metal mixture-induced, olfactory bulb and hippocampal damage by augmenting antioxidant capacity and activation of Nrf2-Hmox-1 signaling in male rats.

PURPOSE/AIM OF THE STUDY: Heavy metals and metalloids have been implicated in neurodenerative diseases. Present study has evaluated the potential protective effects of Se and Zn on heavy metals and metalloids mixture-induced (Cd, Pb, Hg and As) toxicity in the hippocampus and olfactory bulb in male rats. MATERIALS AND METHODS: Five groups of Wistar rats were randomly divided in to: controls, toxic metals mixture (TMM) exposed rats (PbCl2, 20 mg·kg-1; CdCl2, 1.61 mg·kg-1; HgCl2, 0.40 mg·kg-1 and NaAsO3, 10 mg·kg-1)), TMM + Zn, TMM + Se and TMM-+Zn + Se groups and were orally treated for 60 days. RESULTS: We found that in hippocampus and olfactory bulb, TMM generated increased lipid peroxidation and diminished antioxidant capacity. These adverse effects induced by TMM were alleviated by Zn and Se co-treatment; moreover, essential trace elements (Zn and Se) decreased activity of acetylcholinesterase, reduced Cd, Pb, Hg and As bioaccumulation in hippocampus and olfactory bulb and decreased levels of TNF-α in the hippocampus. TMM treated rats had lower levels of Hmox-1 (hippocampus), higher levels of Nrf2 (olfactory bulb and hippocampus) and NF-kB (olfactory bulb). TMM treated rats showed significantly highest time in locating the escape hole. Histopathological examination revealed hypertrophied granule cells in OB of TMM exposed rats. CONCLUSION: Zn and Se supplementation can reverse quaternary mixture-induced (Cd, Pb, Hg and As) toxicity in hippocampus and OB in male albino rats.

Blood donation and heavy metal poisoning in developing nations: Any link?

Long term health effects of heavy metal exposure from both occupational and environmental settings involve multi-organ toxicities including but not limited to disturbances of neurological, cognitive, and metabolic processes, immune system dysregulation, carcinogenesis and sometimes permanent disabilities. Humans are exposed to toxic metals through various sources and routes of entry. The risk of heavy metal poisoning from donor blood has been the subject of many scientific investigations. In this review we highlight how the access to a safe and adequate blood transfusion with minimal risk of toxic metals to recipients is a public health challenge, especially in developing nations. For quality assurance purposes, blood donors are screened for various blood-borne pathogens, but screening for toxic metal levels is not routine. Evidence from scientific studies used in this review lends credence to the risk of heavy metal poisoning from donors with high blood concentrations of these heavy metals. The risk of toxicity is exceptionally high in vulnerable populations such as neonates and preterm infants, as well as in pregnant women and other individuals with conditions requiring multiple blood transfusions. This is worse in developing countries where some members of the population engage in illegal refining and artisanal mining activities. In order to reduce toxic metal exposure in vulnerable populations, blood meant for transfusion in vulnerable subjects, e.g. children, should be routinely screened for heavy metal concentrations. Patients receiving multiple blood transfusions should also be monitored for iron overload and its attendant toxicities.

Selenium and zinc supplementation mitigates metals-(loids) mixture- mediated cardiopulmonary toxicity via attenuation of antioxidant, anti-inflammatory and antiapoptotic mechanisms in female Sprague Dawley rats.

This study evaluated the cardiopulmonary protective effects of essential elements (Zn and Se) against heavy metals mixture (HMM) exposure. Twenty five female Sprague Dawley albino rats, divided in to five groups: controls were orally treated only with distilled water; next, group 2 was exposed to HMM with the following concentrations: 20 mg/kg of Pb body weight, 0.40 mg/kg of Hg, 0.56 mg/kg of Mn, and 35 mg/kg of Al. Groups 3, 4 and 5 were exposed to HMM and co-treated with zinc chloride (ZnCl2; 0.80 mg/kg), sodium selenite (Na2SeO3;1.50 mg/kg) and both zinc chloride and sodium selenite, respectively. The experiment lasted for 60 days. Afterwards animals were sacrificed, and we conduced biochemical and histopathological examination of the heart and lungs. HMM only exposed animals had an increased levels of malondialdehyde (MDA) and nitric oxide (NO), increased IL-6 and TNF-α, attenuated SOD, GPx, CAT and GSH and caspase 3 in the heart and lungs. HMM affected NF-kB and Nrf2 in the heart muscle with histomorphological alterations. Zn and Se attenuated adverse effects of HMM exposure. Essential element supplementation ameliorated heavy metal cardiopulmonary intoxication in rats.

Ameliorative Effects of Zn and Se Supplementation on Heavy Metal Mixture Burden via Increased Renal Metal Excretion and Restoration of Redoxo-Inflammatory Alterations.

Heavy metals (HM)in the environment have provoked global attention because of its deleterious effects. This study evaluated the protection offered by Zn or Se or both against HMM-induced alterations in the kidney. Male Sprague Dawley rats were distributed into 5 groups of 7 rats each. Group I served as normal control with unrestricted access to food and water. Group II received Cd, Pb, and As (HMM) per oral daily for 60 days while groups III and IV received HMM in addition to Zn and Se respectively for 60 days. Group V received both Zn and Se in addition to HMM for 60 days. Metal accumulation in feces was assayed at days 0, 30, and 60 while accumulation in the kidney and kidney weight were measured at day 60. Kidney function tests, NO, MDA, SOD, catalase, GSH, GPx, NO, IL-6, NF-Κb, TNFα, caspase 3, and histology were assessed. There is a significant increase in urea, creatinine, and bicarbonate ions while potassium ions decreased. There was significant increase in renal function biomarkers, MDA, NO, NF-Κb, TNFα, caspase 3, and IL-6 while SOD, catalase, GSH, and GPx decrease. Administration of HMM distorted the integrity of the rat kidney, and co-treatment with Zn or Se or both offered reasonable protection suggesting that Zn or Se could be used as an antidot against the deleterious effects of these metals.

African mesquite elicits neuroprotective activity against quaternary metal mixture -induced olfactory bulb-hippocampal oxido-inflammatory stress via nrf2-hmox-1pathway.

African mesquite AM is widely used as an anti-inflammatory agent in sub-Sahara Africa especially Nigeria. Given its strong anti-inflammatory potency, this study has evaluated the neuroprotective properties of AM in the hippocampus HIP and olfactory bulb OB of rats exposed to Cd, As, Hg, and Pb. Twenty-five albino Sprague Dawley rats were randomly divided into five groups in this experiment. Group 1, the control received only water. Group 2 received heavy metal mixture HMM (PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg), for 60 days. Groups 3, 4, and 5 were treated with HMM along with AM at doses of 500, 1000, and 1500 mg/kg, respectively. AM decreased the Cd, As, Hg, and Pb levels in OB and HIP, restored the activities of antioxidants, Hmox-1, reduced the activities of AChE, NRF2 and NFkB and improved histopathology.

Prosopis africana exerts neuroprotective activity against quaternary metal mixture-induced memory impairment mediated by oxido-inflammatory response via Nrf2 pathway.

The beneficial effects of Prosopis africana (PA) on human health have been demonstrated; however, its protective effects against heavy metals (HM) are not yet understood. This study evaluated the potential neuroprotective effects of PA in the cerebral cortex and cerebellum. To accomplish this, we divided 35 albino Sprague Dawley rats into five groups. Group I did not receive either heavy metal mixture (HMM) or PA. Group II received a HMM of PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg) orally for a period of two months. Groups III, IV, and V received HMM along with PA at doses of 500, 1000, and 1500 mg/kg, respectively. PA caused decreased levels of HM accumulation in the cerebral cortex and cerebellum and improved performance in the Barnes maze and rotarod tests. PA significantly reduced levels of IL-6 and TNF-α. PA increased concentrations of SOD, CAT, GSH, and Hmox-1 and decreased the activities of AChE and Nrf2. In addition, levels of MDA and NO decreased in groups III, IV, and V, along with an increase in the number of live neurons. In conclusion, PA demonstrates a complex neuroprotective effect with the potential to alleviate various aspects of HM-induced neurotoxicity.

Role of Anonychium africanum (Plantae, Fabaceae) in Metal Oxido-Inflammatory Response: Protection Evidence in Gonad of Male Albino Rat.

Male fertility is strongly affected by the overexpression of free radicals induced by heavy metals. The aim of this study was to evaluate the potential antioxidant, anti-inflammatory, and gonado-protective effects of natural compounds. Biochemical and morphological assays were performed on male albino rats divided into five groups: a control group (water only), a group orally exposed to a metal mixture of Pb-Cd-Hg-As alone and three groups co-administered the metal mixture and an aqueous extract of the Nigerian medicinal plant, Anonychium africanum (Prosopis africana, PA), at three different concentrations (500, 1000, and 1500 mg/kg) for 60 days. The metal mixture induced a significant rise in testicular weight, metal bioaccumulation, oxidative stress, and pro-inflammatory and apoptotic markers, while the semen analysis indicated a lower viability and a decrease in normal sperm count, and plasma reproductive hormones showed a significant variation. Parallel phytochemical investigations showed that PA has bioactive compounds like phlobatannins, flavonoids, polyphenols, tannins, saponins, steroids, and alkaloids, which are protective against oxidative injury in neural tissues. Indeed, the presence of PA co-administered with the metal mixture mitigated the toxic metals' impact, which was determined by observing the oxido-inflammatory response via nuclear factor erythroid 2-related factor 2, thus boosting male reproductive health.

Zn and Se abrogate heavy metal mixture induced ovarian and thyroid oxido-inflammatory effects mediated by activation of NRF2-HMOX-1 in female albino rats.

The thyroid is vital for the proper functioning of the female reproductive system since it regulates the metabolism and development of ovary. This is an evaluation of the essential trace elements ETE on the heavy metals mixture HMM mediated oxido-inflammatory effects in the ovary and thyroid of female albino rats. Eight groups (5 female rats /group) were treated as follows for 60 days: Group 1: Deionized water only; Group 2: (Pb, Hg, Mn and Al); Group 3: HMM + ZnCl2, 0.80 mg/kg; Group 4: HMM + Na2SeO3, 1.50 mg/kg; Group 5: HMM + ZnCl2, 0.80 mg/kg and Na2SeO3, 1.50 mg/kg combined. On day 60 animals were euthanized, ovary and thyroid were harvested and used for, MDA, NO, antioxidants, TNF-α, IL-6, HMOX-1, Caspase-3, NF-KB, NRF2, HM and histopathology. There was significant bioaccumulation of Pb, Al, Hg and MN; elevated IL-6 and TNF-α, MDA and NO, caspase-3 and NRF2, NFKB and HMOX-1 with significant decrease in antioxidants in the HMM only group in comparison to the control. Co-treatment with ETE reversed most of these effects. ETE may ameliorate HMM -induced ovarian and thyrotoxicity in female albino rats by blunting oxido-inflammatory activities.

Selenium and zinc alleviate quaternary metal mixture -induced neurotoxicity in rats by inhibiting oxidative damage and modulating the expressions of NF-kB and Nrf2/Hmox-1 pathway.

Background: This study evaluated the potential protective effects of Zn and Se in the cerebellum and cerebral cortex, two fundamentally important brain regions, in albino rats that were exposed to heavy metals mixture (Al, Pb, Hg and Mn). Methods: Animals were divided into five groups of seven animals per group with following patterns of exposure, controls group 1 were orally treated with deionized water for 60 days; group 2 was exposed to heavy metal mixture (HMM) with following concentrations (20 mg·kg-1 of Pb body weight; 0.40 mg·kg-1 of Hg; 0.56 mg·kg-1 of Mn; and 35 mg·kg-1; of Al), while groups 3,4 and 5 were exposed to HMM and orally co-treated with zinc chloride (ZnCl2; 0.80 mg/kg), sodium selenite (Na2SeO3;1.50 mg/kg) and zinc chloride plus sodium selenite (ZnCl0.2 + Na2SeO3) respectively. Results: Exposure to HMM depressed cellular antioxidant apparatus, induced generation of lipid peroxidation markers (Malondialdehyde and NO), downregulated expression of transcription factors (Nrf2, and NF-kB) and upregulated Caspase 3 levels. HMM potentiated acetylcholinesterase activity and induced moderate histopathological alterations. Nevertheless, Zn, Se and in particular Zn + Se had recovering effects on all mentioned hazardous effects produced by HMM exposure in the cerebral cortex and cerebellum. Conclusions: Selenium and zinc exert neuroprotection via Nrf2/NF-kB signaling pathways against quaternary heavy metal mixture-induced impairments in albino Sprague Dawley rats.

Nickel and aluminium mixture elicit memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus of male albino rats.

This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided into four groups. Group 1 (control) received deionized water. Group 2 and 3 received Aluminium (1 mg/kg) and Nickel (0.2 mg/kg) respectively, while Group 4 received Ni and Al mixture HMM three times a week orally for 90 days. Barnes maze tests was performed. Rats were sacrificed under pentobarbital anaesthesia, cerebral cortex and hippocampus were separated, and metal levels were measured using Atomic Absorption Spectroscopy (AAS). Malondialdehyde (MDA), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), Brain Derived Neurotrophic Factor (BDNF), Nerve growth factor NGF, cyclo-oxygenase COX-2 and Acetylcholinesterase (AChE) were assayed using ELISA kits. Ni/Al binary mixture exposed rats showed a shorter latency period (though not significant) of 3.21 ± 1.40 s in comparison to 3.77 ± 1.11 (Ni only) and 3.99 ± 1.16(Al only). Ni/Al mixture gp had the lowest levels of Mg in both the hippocampus and frontal cortex when compared with the individual metals. In the hippocampus Al only exposed rats significantly showed p < 0.05 higher iron and Ca levels in comparison to Ni/Al mixture. Al alone significantly showed p < 0.05 lower levels of Fe but higher Ca than the Ni/Al mixture group. Exposure to Al only showed lower levels of BDNF in comparison to Ni/Al combination, whereas Ni/Al mixture gp had lower levels of NGF in comparison to the individual metals in the hippocampus. In the frontal cortex Ni only, group showed significantly lower BDNF in comparison to Ni/Al mixture whereas the mixture showed significantly lower NGF when compared with Al only group. There were higher levels of COX-2 in the Ni/Al mixture than individual metal treated rats in both hippocampus and frontal cortex. AChE levels in the Ni/Al mixture group was higher than Ni or Al only gps in the hippocampus whereas in the frontal cortex, Ni/Al exposed rats showed significantly lower AChE levels in comparison to Al only group. Ni, Al and Ni/Al mixture exhibited memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus. The BDNF-COX-2 AChE signalling pathway may be involved in the neurotoxicity of Ni and Al.

Essential Trace Elements Prevent the Impairment in the Retention Memory, Cerebral Cortex, and Cerebellum Damage in Male Rats Exposed to Quaternary Metal Mixture by Up-regulation, of Heme Oxygynase-1 and Down-regulation of Nuclear Factor Erythroid 2-related Factor 2-NOs Signaling Pathways.

In the present study, we examined adverse effects of metals and metalloids in the Cerebral cortex (CC) and Cerebellum (CE). Group 1 comprised from the controls while other four groups of male Wistar rats were treated with following pattern: Group II (Heavy Metal Mixture HMM only: PbCl2, 20 mg·kg-1; CdCl2, 1.61 mg·kg-1; HgCl2, 0.40 mg·kg-1, and NaAsO3,10 mg·kg-1), Groups III (HMM + ZnCl2); Group IV (HMM + Na2SeO3) and Group V (HMM + ZnCl2 + Na2SeO3) for 60 days per os. HMM promoted oxidative stress in the CC and CE of treated rats compared to controls; moreover, exposure to HMM led to increased activity of the AChE and pro-inflammatory cytokines; also, HMM promoted accumulation of caspase 3 and other transcriptional factors such as Nrf2 and decreased levels of Hmox-1. Essential metals reduced increased bioaccumulation of Pb, Cd, As and Hg in CC and CE caused by HMM exposure. Also, all mentioned adverse effects were diminished by essential metals treatment (Se and Zn). HMM exposed rats had considerably less escape dormancy than controls. Histopathological analysis revealed moderate cell loss at the intermediate (Purkinje cell) and granular layer. Zinc and selenium supplementations could reverse adverse effects of heavy metals at various cellular levels in neurons.

Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers.

Heavy metals (HMs) such as cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) are highly toxic elements. They are often found together in nature as a heavy metal mixture (HMM) and are known to contribute to subfertility/infertility as environmental pollutants. This study aims to evaluate the potential benefits of treating HMM-induced testicular pathophysiology with zinc (Zn) and/or selenium (Se). Six-week-old male Sprague Dawley rats were grouped into 5 (n = 7). The control group received deionized water, while the other groups were treated with PbCl2 (20 mg kg-1), CdCl2 (1.61 mg kg-1), HgCl2 (0.40 mg kg-1), and Na2AsO3 (10 mg kg-1) in deionized water for 60 days. Additionally, groups III to V received Zn, Se, and Zn/Se, respectively, for 60 days. The study evaluated testis weight, metal accumulation, sperm analysis, FSH, LH, testosterone, prolactin, oxidative stress, antioxidants, pro-inflammatory and apoptotic markers, and presented structural changes in the testis as micrographs. HMM caused a significant increase in testis weight, metal accumulation, prolactin, oxidative stress, and pro-inflammatory and apoptotic markers, while significantly decreasing semen analysis, FSH, LH, and testosterone. Histology showed decreased spermatogenesis and spermiogenesis, as evidenced by the structure of the germ cells and spermatids. However, Zn, Se, or both ameliorated and reversed some of the observed damages. This study provides further evidence for the mitigative potential of Zn, Se, or both in reversing the damage inflicted by HMM in the testis, and as a countermeasure towards improving HM-induced decrease in public health fecundity.

Ni and Al mixture amplifies cerebellar oxido-inflammatory responses, down regulates AChE and BDNF/NGF levels in motor impairment in male albino rats.

BACKGROUND: Aluminum and nickel are potent neurotoxicants to which humans are constantly exposed. Previous studies have demonstrated that these two metals can affect the motor system, but their effects on the cerebellum, a central nervous system region with the highest number of neurons, have remained largely unexplored. Therefore, we conducted a study to investigate the adverse effects of Al, Ni, and Al+Ni in vivo. METHODS: In our study, seven male Sprague Dawley rats per group were orally exposed to deionized water, 0.2 mg/kg of Ni, 1 mg/kg of Al, and 0.2 mg/kg of Ni + 1 mg/kg of Al (as a binary heavy metals mixture; HMM), respectively. RESULTS: Ni, Al, and HMM exposed rats accumulated higher levels of Al and Ni compared to controls, and HMM treated animals had higher levels of Ca and Fe in the cerebellum (p < 0.05). Malondialdehyde (MDA) levels were significantly (p < 0.05) higher in the HMM, Ni, and Al treated groups compared to the control group that received deionized water. Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx) activities were significantly (p < 0.05) reduced in the HMM, Ni, and Al treated groups compared to the control group that received deionized water. Ni, Al, and HMM significantly (p < 0.05) shortened the length of time of the grip in comparison to the control. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels were significantly decreased in the nickel, Al, and heavy metal mixture groups compared with the control group. Moreover, there was a significant decrease in the activity of acetylcholinesterase (AChE) and a increase in cyclooxygenase-2 (COX-2) activity in the Ni, Al, and HMM treated groups compared to the control group. CONCLUSION: HMM exposed animals had significantly poorer performance in the Rotarod test (p < 0.05) than controls. Al and Ni induced impairment of cerebellar function at various levels.

Dietary interventions for autism spectrum disorder: An updated systematic review of human studies.

Autism is a complex spectrum of disorders with genetic, epigenetic, autoimmune, oxidative stress, and environmental etiologies. Treatment of ASD using dietary approach is a promising strategy, especially owing to its safety and availability. Our study critically analysed the roles and efficacy of antioxidants, probiotics, prebiotics, camel milk and vitamin D. This systematic review provides an updated synopsis of human studies that investigated therapeutic benefits of these dietary interventions in autism. A total of 943 papers were identified out of which 21 articles were included in the systematic review. The selected studies investigated the impact of 5 different dietary supplementations in ASD symptom and behaviours. These agents include; antioxidants/polyphenolic compounds, probiotics, prebiotics, camel milk and vitamin D. From the results of the present review, antioxidants/polyphenolic compounds decreased the levels of inflammatory cytokines and improved behavioural symptoms. Probiotics improved behavioural and GI symptoms as well as restored gut microbiota equilibrium. Prebiotics decreased levels of inflammatory cytokines, improved behavioural and GI symptoms and improved gut microbiota. Vitamin D improved behavioural symptoms and offered protective effects against neurotoxicity. Camel milk reduced inflammatory responses and oxidative stress. Given the chronic nature as well as early onset of ASD, dietary supplements become useful to complement nutritional deficiencies in children with ASD. Key benefits of these agents stem from their ability to target multiple physiological areas via the gut brain-axis and are devoid of potential harmful or aggravating effects on ASD patients. The evidence collated in this review propose that dietary intervention may provide a new platform for the management of autism.

Association of autism with toxic metals: A systematic review of case-control studies.

Environmental factors have been associated with the etiology of autism spectrum disorder ASD in recent times. The involvement of toxic metals in the generation of reactive oxygen species and their epigenetics effects have been implicated in ASD. This systemic review examines the association of toxic metals with autism in children. A systematic literature search was performed in scientific databases such as PubMed, Google scholar, and Scopus. Case-control studies evaluating toxic metal levels in different tissues of ASD children and comparing them to healthy children (control group) were identified. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of the included studies. Six case-control studies with 425 study subjects met our inclusion criteria. A total of four studies indicated higher levels of As, Pb, Hg, Cd, Al, Sn, Sb, Ba, TI, W, and Zr in whole blood, RBC, in whole blood, RBC, and hair samples of children with autism compared with control suggestive of a greater toxic metal exposure (immediate and long-term). Three studies identified significantly higher concentrations of Cd, Pb and Hg in urine and hair samples of autistic children compared to control suggesting decreased excretion and possible high body burden of these metals. The findings from this review demonstrate that high levels of toxic metals are associated with ASD, therefore, critical care is necessary to reduce body burden of these metals in children with ASD as a major therapeutic strategy.

Zinc and selenium mitigated heavy metals mixture (Pb, Al, Hg and Mn) mediated hepatic-nephropathy via modulation of oxido-inflammatory status and NF­kB signaling in female albino rats.

This study evaluated the protective role o of zinc and selenium on heavy metal mixture (HMM) induced hepatic-nephropathy. Twenty-five female Wistar albino rats were weight-matched and divided into five groups of five female rats each. Group 1(control) received deionized water only. Group 2 received heavy metal mixture HMM (20 mg·kg-1 of Pb, 0.40 mg·kg-1 of Hg, 0.56 mg·kg-1 of Mn and 35 mg·kg-1 of Al). Groups 3, 4 and 5 were co-administered with metal mixtures and Zn, Se and Zn + Se respectively. Treatments were through oral gavage for 60 days; animals were sacrificed under pentobarbital and liver and kidney harvested for tests. Zn, Se and Zn + Se reduced metal accumulation in the liver and kidney. HMM exposure caused non-significant increase in AST, ALP, ALT and TP, but significant increase in IL-6 and TNF -α, Nf-kB, Hmox-1, Nfr2, MDA and NO when compared to the control. Essential trace elements significantly decreased IL-6 and TNF -α, Nf-kB, Hmox-1and Nfr2 in comparison to HMM only group. Treatment with Zn, Se and Zn + Se significantly reversed the HHM mediated decreased SOD levels. HMM triggered degenerative changes in the central vein, showed vacuolations with connective tissues fragmentation and lymphocytes infiltration were reversed by essential trace elements. Essential trace elements supplementation is protective against HMM mediated hepato-renal impairment.

Banana peel ameliorated hepato-renal damage and exerted anti-inflammatory and anti-apoptotic effects in metal mixture mediated hepatic nephropathy by activation of Nrf2/ Hmox-1 and inhibition of Nfkb pathway.

This study evaluated the protective role of banana peel extract (BP) on heavy metal mixture (HMM) mediated hepatorenal toxicity using a rat model. Twenty-five female Wistar albino rats were weight-matched and divided into five groups of five female rats each. Group 1(control) received deionized water only. Group 2 received HMM only (20 mg kg-1 of Pb, 0.40 mg kg-1 of Hg, 0.56 mg kg-1 of Mn and 35 mg kg-1 of Al). Groups 3, 4 and 5 were co-administered with the same metal mixture with BP at 200, 400 and 800 mg kg-1, respectively. Treatments were through oral gavage for 60 days; animals were sacrificed pentobarbital anesthesia and liver and kidney harvested for test. Thereafter, metal levels, malondialdehyde (MDA) and nitric oxide (NO), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPx), interlukin-6 (IL-6) and tumor necrosis alpha (Tnf-α), caspase-3 (Cas-3), Nuclear factor kappa B (Nfkb), Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (Hmox-1) were assayed. HMM group presented higher levels of metal, IL-6 and Tnf-α, MDA, NO, Nfkb and Hmox-1 in HMM group which were significantly reduced by BP. BP was protective against metal mixture induced histopathological distortions. HMM exposure significantly distorted hepatorenal functions and BP treatment reduced metal bioavailability and abrogated most of these alterations.