Caffeic acid attenuates memory dysfunction and restores the altered activity of cholinergic, monoaminergic and purinergic in brain of cadmium chloride exposure rats.

OBJECTIVES: This study aims to evaluate the neuroprotective effect of caffeic acid (CAF) against cadmium chloride (CdCl2) in rats via its effect on memory index as well as on altered enzymatic activity in the brain of CdCl2-induced neurotoxicity. METHODS: The experimental rats were divided into seven groups (n=6 rats per group) of healthy rats (group 1), CdCl2 -induced (CD) (3 mg/kg BW) rats (group 2), CD rats + Vitamin C (group 3), CD rats + CAF (10 and 20 mg/kg BW respectively) (group 4 & 5), and healthy rat + CAF (10 and 20 mg/kg BW respectively) (group 6 & 7). Thereafter, CdCl2 and CAF were administered orally to the experimental rats in group 2 to group 5 on daily basis for 14 days. Then, the Y-maze test was performed on the experimental rats to ascertain their memory index. RESULTS: CdCl2 administration significantly altered cognitive function, the activity of cholinesterase, monoamine oxidase, arginase, purinergic enzymes, nitric oxide (NOx), and antioxidant status of Cd rats (untreated) when compared with healthy rats. Thereafter, CD rats treated with vitamin C and CAF (10 and 20 mg/kg BW) respectively exhibited an improved cognitive function, and the observed altered activity of cholinesterase, monoamine oxidase, arginase, purinergic were restored when compared with untreated CD rats. Also, the level of brain NOx and antioxidant status were significantly (p<0.05) enhanced when compared with untreated CD rats. In the same vein, CAF administration offers neuro-protective effect in healthy rats vis-à-vis improved cognitive function, reduction in the activity of some enzymes linked to the progression of cognitive dysfunction, and improved antioxidant status when compared to healthy rats devoid of CAF. CONCLUSIONS: This study demonstrated the neuroprotective effect of CAF against CdCl2 exposure and in healthy rats.

Cornus officinalis var. koreana Kitam extracts alleviate cadmium-induced renal fibrosis by targeting matrix metallopeptidase 9.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis var. koreana Kitam (Cornus officinalis) is a commonly used Chinese herbal medicine and has a good clinical efficacy in kidney and liver diseases. Recent years, a number of studies reported the significant effects of Cornus officinalis on renal fibrosis. However, it is still unclear about the underlying specific mechanism, the bioactive ingredients, and the target gene regulatory network. AIM OF THE STUDY: We investigated the impact of Cornus officinalis extract on cadmium-induced renal fibrosis, screened the bioactive ingredients of Cornus officinalis using a pharmacological sub-network analysis, and explored the regulatory effects of Cornus officinalis extracts on target gene matrix metallopeptidase 9 (MMP9). METHODS: Male C57BL/6N mice were treated with single or combinatorial agents such as saline, cadmium chloride, Cornus officinalis, Isoginkgetin and FSL-1. Isoginkgetin is a compound with anti-MMP9 activity. FSL-1 can induce MMP9 expression. Masson staining and Western blot and immunohistochemistry analyses were used for assessing renal fibrosis. In addition, wound healing model was established using BUMPT (Boston university mouse proximal tubular) cells to investigate how Cornus officinalis affected cadmium-induced cell migration. The main Cornus officinalis bioactive compounds were identified by UHPLC-MS (Ultra-high-performance liquid chromatography - mass spectrometry). The MMP9 target for Cornus officinalis active ingredients were confirmed through a pharmacological sub-network analysis. RESULTS: Aqueous extracts of Cornus officinalis protected from renal dysfunction and kidney fibrosis induced by cadmium chloride in mice. In vitro experiments validated that Cornus officinalis extracts inhibited cell migration ability especially in cadmium chloride condition. The sub-network analysis and chemical components profiling technique revealed the active compounds of Cornus officinalis. Cellular thermal shift assay verified the binding abilities of three active components Daidzein, N-Acetyl-L-tyrosine or Swertisin with matrix metalloproteinase-9. Gelatin zymography assay revealed that the activity of MMP9 was inhibited by the three active components. We further confirmed that MMP9 was involved in the process of Cornus officinalis extracts reducing renal fibrosis. Cornus officinalis attenuated the cadmium-induced renal fibrosis was correlated with decreased expression of MMP9, collagen I, α-SMA (alpha-smooth muscle actin) and vimentin. CONCLUSIONS: This study demonstrated that Cornus officinalis extracts could alleviate the cadmium chloride-induced renal fibrosis by targeting MMP9, and might provide new insights into the mechanism of treating renal fibrosis by Cornus officinalis.

Effect of lactoferrin supplement on cadmium chloride induced toxicity to male rats: Toxicopathological, ultrastructural and immunological studies.

This study sought to determine whether lactoferrin supplementation could counteract the harm that cadmium (Cd) induced to the rats. The effect of Cd and lactoferrin were investigated in hematological, biochemical, histological, immunohistochemical expression and ultrastructural studies. After 30 days of treatment, rats exposed to Cd had significantly higher levels of Cd in their blood, more oxidized lipids, and less antioxidant capacity overall. Supplemental lactoferrin also significantly undoes that effect. Hematological and biochemical parameters changed along with the increase in blood Cd levels. The histological integrity of the liver, kidney, spleen, and (axillary, cervical, mesenteric and popliteal) lymph nodes that had been damaged by Cd exposure was also restored by lactoferrin supplementation. Moreover, the liver and spleen ultrastructure showed the same improvement. In addition, the spleen of Lf/Cd group showed less immunohistochemical expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in comparison to the Cd group. In conclusion, the current study showed that supplementing with lactoferrin improved immune response and restored biochemical and oxidative stability induced by Cd.

Nephroprotective effect of Physalis peruviana L. calyx extract and its butanolic fraction against cadmium chloride toxicity in rats and molecular docking of isolated compounds.

BACKGROUND: Cadmium is an environmentally toxic metal that has deleterious effects on both animals and humans due to its accumulation in different body tissues. Physalis peruviana L. fruit and calyx contain many active constituents which are used traditionally for their different biological activities. Based on the traditional uses of P. peruviana L. calyx, we aimed to evaluate the nephroprotective effect of their 80% aqueous methanol extract (AME) and n-butanol fraction (Bu.F.) against cadmium chloride-induced nephrotoxicity in rats and to correlate this activity with phytoconstituents isolated using molecular docking studies. METHODS: The n-butanol fraction of P. peruviana L. calyx was fractionated using various chromatographic techniques and the isolated compounds were identified based on their chemical and spectroscopic data. The nephroprotective activity was assessed using cadmium chloride-induced nephrotoxicity in the rat model, by measuring some important parameters such as body weight, kidney weight, serum urea, and creatinine levels, oxidative stress markers, inflammatory markers, and histopathological examinations of kidney tissue. Molecular docking studies of the isolated compounds were performed. RESULTS: Three withanolides named 4 ß-hydroxywithanolide E (1), Physalin B (2) and 3α, 14ß-dihydroxywithaphysalin N (3) were isolated and identified from the n-butanol fraction of P. peruviana L calyx extract. The extract and its butanol fraction significantly improved the serum kidney function markers and tissue oxidative status including malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT). Additionally, the extracts significantly decreased the levels of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappaB (NF-κß). Moreover, the histological changes were ameliorated by the extracts. The molecular docking study showed that the isolated compounds displayed a remarkable inhibitory activity against IκB kinase. CONCLUSION: The AME and its butanol fraction of P. peruviana L calyx showed potential nephroprotective activity against cadmium chloride-induced nephrotoxicity which is correlated at least in part to its considerable withanolides content.

Evaluation of Hepatoprotective Efficacy of a Polyherbal Unani Formulation Majoon-Najah against Cadmium Chloride-induced Liver Damage.

BACKGROUND: Majoon-Najah is a composite Unani formulation that consists of multiple medicinal plants and is advised for neurological illnesses. Several studies were carried out on Majoon-Najah (MN) and its ingredients to evaluate the protective effect against seizure and antidepressant activity in animals using a classical form as well as extract. Terminalia bellerica and Emblica officinalis are the major constituents of MN. Scientifically documented literature summarises the hepatoprotective potential of these constituents. AIM: The current study aimed to evaluate the possible hepatoprotective, antioxidant and antiinflammatory perspective of traditional Indian Unani formulation MN and Majoon-Najah hydroalcoholic extract (MNHE) in a Guinea pig model. METHODS: Thirty adult male albino guinea pigs were randomly assigned into five groups for this study. MN and MNHE were given intragastrically for 15 days, followed by intraperitoneal Cadmium chloride (CdCl2, 3 mg/kg/day) from days 8 to 15, as per the schedule. Blood samples were taken from the heart on the 16th day, and the liver was operated on for biochemical analysis and histopathology under complete anesthesia. RESULTS: CdCl2 changed the levels of liver function markers, serum biochemical indicators like albumin, total protein, glucose, and cholesterol in the blood; lipid peroxidation (MDA), glutathione reductase (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) in hepatic tissue homogenate, pro-inflammatory cytokines level and liver cytoarchitecture. MN and MNHE were found to protect guinea pigs' liver from CdCl2-induced injury by lowering raised parameters and increasing enzymatic antioxidants. MN and MNHE did not significantly heal injured liver tissues caused by CdCl2 in histopathological examinations. CONCLUSION: CdCl2 induces hepatotoxicity that is likely to worsen with increasing dosage and duration of exposure. MN and MNHE exert their hepatoprotective action by scavenging free radicals, decreasing malondialdehyde levels, activating antioxidant enzymes, and down-regulating proinflammatory indicators.

An assessment of the ameliorative role of hesperidin in Drosophila melanogaster model of cadmium chloride-induced toxicity.

Cadmium chloride (CdCl2) is an important heavy metal widely regarded as an environmental contaminant. Hesperidin, a flavanone glycoside found in citrus fruits, has an established properties against free radicals, apoptosis, and inflammation. The present study investigated the protective actions of hesperidin on CdCl2-induced oxidative damage and inflammation in Drosophila melanogaster. For 7 consecutive days via their diet regimen, the flies were exposed to CdCl2 alone (0.05 mM) or in combination with hesperidin (50 and 100 µM). Exposure to CdCl2 significantly (p < 0.05) increased mortality rate of flies, whereas the survived flies demonstrated significant oxidative toxicity from decreased activities of catalase and Glutathione S-transferase (GST) and Total Thiol (T-SH) and Non-Protein Thiols (NPSH) levels as well as accumulation of Nitric Oxide (NO (nitrite/nitrate)), protein carbonyl and Hydrogen Peroxide (H2O2). However, hesperidin-supplemented diet improved Acetylcholinesterase (AChE) activity, mitochondrial metabolic rate (cell viability), locomotor activity, and amelioration of oxidative damage and lipid peroxidation induced by CdCl2. The hesperidin diet supplement boosted the antioxidant milieu and ameliorated the oxidative damage in the treated flies. Overall, the findings revealed that hesperidin improved antioxidative protective capacity in Drosophila melanogaster model of CdCl2-induced toxicity. This suggests hesperidin as a potential therapeutic agent against oxidative stress disorders due to exposure to CdCl2 and or related toxicants.

Cadmium-induced preeclampsia-like phenotype in the rat is related to decreased progesterone synthesis in the placenta.

Cadmium (Cd) is a toxic element, which is associated with preeclampsia (PE).We treated pregnant rats with cadmium chloride from gestational days (GDs) 9-12 to introduce the PE-like animal model. Maternal systolic blood pressures (SBPs) and body weights were measured on GDs 0, 5, 10, 15, and 20. Foetuses were delivered by Caesarean section on GD20. Then, the dams were sacrificed and the specimens were obtained. The morphological analysis of the placentae was carried out by haematoxylin and eosin staining examination and immunohistochemistry assay.Our study showed that Cd-treated rats developed PE-like phenotypes, such as hypertension, albuminuria, and foetal growth restriction. Moreover, Cd-injected rats displayed abnormal placental angiogenesis and lower progesterone (P4) levels. We further demonstrated that Cd also inhibited the mRNA and protein expressions of steroidogenic acute regulatory protein, cytochrome P450 cholesterol side-chain cleavage enzyme (CYP11A1), and 3ß-hydroxysteroid dehydrogenase 1 (3ß-HSD1), which are involved in P4 synthesis in the rat placenta.Our study demonstrates that maternal Cd exposure disrupts the local synthesis of P4 in the placenta, which contributes to the onset of PE in pregnant rats. Supplementing P4 at the early gestational stage may be a promising therapeutic strategy to prevent PE, which requires further investigation.

Gallic and ascorbic acids supplementation alleviate cognitive deficits and neuropathological damage exerted by cadmium chloride in Wistar rats.

Cadmium is a highly neurotoxic heavy metal that interferes with DNA repair mechanisms via generation of reactive oxygen species. The potentials of polyphenols and antioxidants as effective protective agents following heavy metal-induced neurotoxicity are emerging. We therefore explored the neuroprotective potentials of gallic and ascorbic acids in CdCl2-induced neurotoxicity. Seventy-two Wistar rats were divided into six groups. Group A received distilled water, B: 3 mg/kg CdCl2, C: 3 mg/kg CdCl2 + 20 mg/kg gallic acid (GA), D: 3 mg/kg CdCl2 + 10 mg/kg ascorbic acid (AA), E: 20 mg/kg GA and F: 10 mg/kg AA orally for 21 days. Depression, anxiety, locomotion, learning and memory were assessed using a battery of tests. Neuronal structure and myelin expression were assessed with histological staining and immunofluorescence. The Morris Water Maze test revealed significant increase in escape latency in CdCl2 group relative to rats concurrently treated with GA or AA. Similarly, time spent in the target quadrant was reduced significantly in CdCl2 group relative to other groups. Concomitant administration of gallic acid led to significant reduction in the durations of immobility and freezing that were elevated in CdCl2 group during forced swim and open field tests respectively. Furthermore, GA and AA restored myelin integrity and neuronal loss observed in the CdCl2 group. We conclude that gallic and ascorbic acids enhance learning and memory, decrease anxiety and depressive-like behavior in CdCl2-induced neurotoxicity with accompanying myelin-protective ability.

Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity.

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl2-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl2 treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl2, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl2-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca2+-CaMKII-dependent Akt/mTOR pathway.

Ficus natalensis extract alleviates Cadmium chloride-induced testicular disruptions in albino rats.

BACKGROUND: Cadmium is a potential environmental pollutant with worldwide health problems. Many Ficus species are reported to have an extensive diversity of traditional uses, among them the treatment of reproductive toxicity. OBJECTIVES: This study set out to evaluate the effect of Ficus natalensis extract on the testicular impairments induced by cadmium chloride (CdCl2) and investigated the potential mechanisms associated with its treatment. METHODS: Thus, 40 male albino rats were categorized into 4 groups (n = 10); group I (control), group II (cadmium-treated group) orally received 5 mg/kg/day CdCl2 for one month, group III (cadmium + Ficus natalensis extract) orally received 5 mg/kg/day CdCl2 for one month plus 200 mg/kg/day Ficus natalensis extract for another month, and group IV (cadmium + reference drug (mesterolone) orally received 5 mg/kg/day CdCl2 for one month plus 4.16 mg/kg/day mesterolone for another month. RESULTS: At the end of experiment, CdCl2 administration markedly induced histological and histo-morphometric changes with a substantial (p < 0.05) decrease in the sperm count, sperm motility, serum TAC, serum testosterone, downregulation in the mRNA expression levels of testicular 17ß-HSD and StAR, in addition to a significant increase in serum TNF-α and testicular MDA level compared to the control group. Conversely, the treatment with Ficus natalensis methanolic extract as well as the reference drug significantly ameliorated the above-mentioned adverse effects induced by CdCl2. CONCLUSIONS: Our results suggested that Ficus natalensis extract can attenuate the CdCl2-induced testicular impairments via inhibiting the oxidative cell damage and inflammation that contributed to CdCl2 toxicity.

Pharmacological and ameliorative effects of Withania somnifera against cadmium chloride-induced oxidative stress and immune suppression in Nile tilapia, Oreochromis niloticus.

This study was carried out to evaluate the effects of dietary supplementation of aqueous extract of Withania somnifera (W. somnifera) against cadmium chloride-induced toxicity in the Nile tilapia, Oreochromis niloticus. Five experimental groups were designed: group (I) was free from cadmium chloride and W. somnifera and served as a control, group (II) was exposed to 1.775 mg L-1 of cadmium chloride only (which is equivalent to 1/4 96-h LC50), while groups (III), (IV), and (V) were exposed to 1.775 mg cadmium chloride L-1 with co-supplementation of dietary W. somnifera in doses of 1.0, 2.0, and 3.0 mL kg-1 body weight (bwt), respectively. The experiment lasted for 4 weeks. In the second and fourth weeks of the experiment, the following indicators were evaluated: hematological (hemogram and blood protein profile), biochemical (activities of serum liver enzymes, namely alanine transaminase (ALT) and aspartate transaminase (AST)), immunological (immunoglobulin M (IgM), serum lysozyme), and tissue antioxidant changes (malondialdehyde (MDA) levels and activities of catalase (CAT) and superoxide dismutase (SOD)). Additionally, gene expressions of glutathione-S-transferase (GST) in the liver were assessed. At the end of the experiment, all fish in all groups were experimentally challenged with Aeromonas hydrophila and the relative protection survival (RPS) was demonstrated. The results revealed that groups exposed to cadmium chloride toxicity and co-supplemented with dietary aqueous extract of W. somnifera at high doses showed significant ameliorative effects in hemogram parameters, total protein, globulin, IgM, and lysozyme against cadmium chloride-induced toxicity compared to the control group and the group exposed to a sublethal dose of cadmium chloride without co-suplemntation of W. somnifera. The results showed also that groups supplemented orally with W. somnifera at high doses have higher antioxidant activities of CAT and SOD and reduction of MDA formation. Levels of gene expressions of GST in the liver were higher in W. somnifera extract-supplemented groups more than those in the group exposed to cadmium chloride-induced toxicity without W. somnifera supplementation. In addition, the results revealed improved RPS with the dietary supply of W. somnifera extract in high doses. In conclusion, this study showed that the dietary supplementation of W. somnifera extract to diets of O. niloticus could be suggested as an effective way to overcome cadmium chloride-induced toxicity because it improves blood parameters and antioxidants, and it can be used as an immunostimulant against the invading bacterial pathogens.

Aqueous-alcoholic Ferulla extract reduces memory impairments in rats exposed to cadmium chloride.

INTRODUCTION: Cadmium (Cd) is the most dangerous heavy metal that is becoming more widespread in nature as a result of industrial activities. One of the toxic effects of Cd on the body is its neurological effect. The mechanism of these effects has been attributed to the induction of oxidative stress. Ferulla plant has antioxidant properties. In the present study, the aim was to reduce the toxic effects of Cd on memory impairment in rats by through the consumption of Ferulla extract. MATERIALS & METHOD: Rats were randomly divided into five groups of six: (1) control group, (2) 300 µM cadmium exposure group, and three treatment groups with doses of (3) 100, (4) 300, and (5) 600 mg/kg.BW of F. Ferulla extract after Cd exposure. To induce neurotoxicity, Cd was daily injected peritoneally at a concentration of 300 µM in 1 ml of normal saline for a week. Next, for 3 weeks, the Cd group received 1 ml of normal peritoneal saline, and the treatment groups received F. Ferulla extract at concentrations of 100, 300, and 600 mg/kg.BW in 1 ml of normal saline daily for a week. At the end of the treatment period, a water maze was used to assess memory disorders. Malondialdehyde (MDA), glutathione concentration (GSH), and glutathione peroxidase (GPX) activity in nerve tissue were also measured. Morris water maze was also performed after intervention. RESULTS: Cd-induced neurotoxicity was shown in Cd groups. MDA, GSH, and GPX have a significant difference in comparison between the Cd and 300, 600 treated groups. MDA has a significant increase (p < 0.05), and GSH and GPX have a significant decrease (p < 0.05). The results of the Morris water maze showed that the Cd group spent either 300 or 600 more distances and time to find a place to escape, which was significant (p < 0.05) CONCLUSION: Cd exposure can induce neurotoxicity and disrupt learning and memory. On the other hand, Ferulla extract can improve learning and memory in Cd-induced neurotoxicity model via induced antioxidant defense system.

Potential antioxidant effects of Narcissus tazetta phenolic compounds against cadmium chloride-induced hepatotoxicity in Swiss albino mice.

Narcissus tazetta (Amaryllidaceae) is a medicinal plant widely used for cut flowers and potted ornamental plant in Tunisia flora. The current study evaluated the phenolic composition and antioxidant properties of its flower extracts and investigated its potential protective activity against cadmium chloride (CdCl2)-induced hepatotoxicity in mice. Mice were divided into six groups of six each: group 1, serving as negative controls, received by intraperitoneal way only distilled water; group 2 received by intraperitoneal way CdCl2 (0.16 mg/kg bw); groups 3 and 4 received CdCl2 at the same dose of group 2 and 100 or 200 mg/kg bw of Narcissus tazetta flower extracts via oral route; groups 5 and 6, serving as positive controls, received only Narcissus tazetta flower extracts. Polyphenolic compounds of the extract were analyzed by colorimetric and high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. Total antioxidant activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging potential of the extract were estimated using colorimetric method. Results indicated that ethanolic flower extract contained high levels of total phenolic and flavonoid along with a strong total antioxidant and DPPH free radical scavenging activities. HPLC-MS analysis identified eight phenolic compounds, including rutin, kaempferol glycosides, and chlorogenic acids. The extract also exhibited marked hepatoprotective effects against CdCl2 toxicity by reducing hepatic levels of malondialdehyde, advanced oxidation protein products, hydrogen peroxide, metallothioneins, and DNA degradation. Additionally, co-administration of Narcissus tazetta flower extracts lowered the plasma activities of transaminases, gamma glutamyl transpeptidase, and lactate dehydrogenase and increased hepatic levels of reduced glutathione, nonprotein thiols, vitamin C, and catalase activity. The hepatoprotective effects of the extract were demonstrated by histopathological improvement of liver disorders. The current study provided ethnopharmacological application of Narcissus tazetta flower extracts against CdCl2-induced oxidative stress, suggesting its chemoprevention role of its phenolic compounds as a natural antioxidant.

Aqueous extract of Adansonia digitata prevents Cadmium Chloride-induced testicular damage in Wistar Rats.

OBJECTIVES: The role of aqueous extract of Adansonia digitata was investigated against cadmium chloride-induced testicular damage in Wistar Rats. METHODS: Thirty (30) male Wistar Rats weighing (150-170) were divided into six groups (n=5). Group A served as control and received oral administration of phosphate buffer saline; group B received 800 mg/kg A. digitata only; group C were injected intraperitoneally with single dose 2 mg/kg b.w cadmium chloride; group D were injected intraperitoneally with single dose 2 mg/kg b.w cadmium chloride and treated with 800 mg/kg aqueous extract of A. digitata; group E received 300 mg/kg vitamin E only; group F were injected intraperitoneally with single dose 2 mg/kg b.w cadmium chloride and treated with 300 mg/kg vitamin E. After 21 days, the animals were sacrificed by cervical dislocation, the testes were excised fixed in Bouins fluids for histological analysis and the other homogenized in 5% sucrose solution for determination of tissue malondialdehyde (MDA) and antioxidant enzyme activity, biochemical assay. RESULTS: The group treated with cadmium chloride plus A. digitata caused significant decrease in MDA levels with significant increase (p<0.05) in antioxidant activities and biochemical enzymes when compared to cadmium chloride only group. CONCLUSIONS: Aqueous extract of A. digitata appears to have ameliorative effect against cadmium chloride-induced testicular damage. This could be attributed to the presence of polyphenolic compound.

Immunohistochemical, histopathological, and biochemical studies of the NF-Ò¡B P65 marker in rat ovaries experimentally intoxicated by cadmium and the protective effect of the purslane plant extract.

The aim of this study is to describe the existence of the inflammatory marker nuclear factor kappa light chain B lymphocyte protein (NF-Ò¡B P65) in the tissue as a response to cadmium (CdCl2) toxicity. Next is to describe the disappearance of the NF-Ò¡B P65 in response to the purslane plant treatment to explore its anti-inflammatory effect, also describing the histopathological and biochemical changes that occurred from CdCl2 toxicity and the purslane plant tissue protections. There are four experimental groups, 32 rats (n = 8) intraperitoneally injected with CdCl2 and orally administered with purslane plant extract (according to groups) for 30 days: group one (control), group two (purslane extract 2 g/kg bw), group three (CdCl2 3.5 mg/kg bw), group four (CdCl2 3.5 mg/kg bw + purslane plant extract 2 g/kg bw). The biochemical findings showed that ovaries and brain tissue homogenates in group three showed malondialdehyde increase and reduction in catalase, total antioxidant capacity, and acetylcholine esterase. A reduction in serum LH, FSH, and estradiol were also recorded. These parameters became normal in group four. The histopathological findings exhibited that group three showed ovarian and cerebral hemorrhage and lung pneumonia. Tissues of group four were protected and no pathological lesions were detected. The immunohistochemical results showed that the inflammatory marker NF-Ò¡B P65 in group three was strongly detected in the spleen and moderately detected in the ovaries, brain, and lung but negatively detected in the tissues of group four. In conclusion, CdCl2 induced ovarian toxicity and the NF-Ò¡B P65 existence was increased. Purslane plant protected rats from CdCl2 toxicity and decrease NF-Ò¡B P65.

Prepubertal exposure to high dose of cadmium induces hypothalamic injury through transcriptome profiling alteration and neuronal degeneration in female rats.

Cadmium (Cd) is a toxic metal, which seems to be crucial during the prepubertal period. Cd can destroy the structural integrity of the blood-brain barrier (BBB) and enters into the brain. Although the brain is susceptible to neurotoxicity induced by Cd, the effects of Cd on the brain, particularly hypothalamic transcriptome, are still relatively poorly understood. Therefore, we investigated the molecular effects of Cd exposure on the hypothalamus by profiling the transcriptomic response of the hypothalamus to high dose of Cd (25 mg/kg bw/day cadmium chloride (CdCl2)) during the prepubertal period in Sprague-Dawley female rats. After sequencing and annotation, differential expression analysis revealed 1656 genes that were differentially expressed that 108 of them were classified into 37 transcription factor (TF) families. According to gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, these differentially expressed genes (DEGs) were involved in different biological processes and neurological disorders including Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), prolactin signaling pathway, PI3K/Akt signaling, and dopaminergic synapse. Five transcripts were selected for further analyses with Real-time quantitative PCR (RT-qPCR). The RT-qPCR results were mostly consistent with those from the high throughput RNA sequencing (RNA-seq). Cresyl violet staining clearly showed an increased neuronal degeneration in the dorsomedial hypothalamus (DMH) and arcuate (Arc) nuclei of the CdCl2 group. Overall, this study demonstrates that prepubertal exposure to high doses of Cd induces hypothalamic injury through transcriptome profiling alteration in female rats, which reveals the new mechanisms of pathogenesis of Cd in the hypothalamus.

Xylopia aethiopica ethanol seed extract suppresses Cadmium chloride-induced ovary and gonadotropins toxicity in adult female Wistar rats.

OBJECTIVE: Xylopia aethiopica is a common plant in West Africa, with wide applications in trado-medical management of several diseases. Thus, our study aimed to analyze the histology and hormonal effects of ethanol extracts of Xylopia aethiopica seeds on cadmium chloride-induced reproductive dysfunction in female Wistar rats. METHODS: We used twenty-five rats weighing 120-150g for this study. The rats were divided into five groups (n=5). Group 1: received only distilled water orally; Group 2: received 2 mg/kg cadmium chloride orally; Group 3: received 2 mg/kg cadmium chloride plus 50 mg/kg Xylopia aethiopica seeds orally; Group 4: received 2 mg/kg cadmium chloride plus 100 mg/kg Xylopia aethiopica seeds orally, and Group 5: received 100 mg/kg Xylopia aethiopica seeds only, orally. We administered the extracts for 14 days, after which we slaughtered the animals following chloroform anesthesia. We took the blood samples by cardiac puncture for hormonal assay. The ovaries and uterus were harvested for histology. We analyzed the data using ANOVA, and the differences in mean values were considered significant at p<0.05. RESULTS: The body weight of the rats showed a dose-dependent reduction (p<0.05), compared with the controls. Xylopia aethiopica seeds significantly (p<0.05) reversed the detrimental effects of Cadmium on LH and FSH. The histological analysis of the ovary showed significant improvement upon treatment with Xylopia aethiopica extract in a dose-dependent manner. CONCLUSIONS: The ameliorative effects of Xylopia aethiopica against cadmium chloride-induced reproductive toxicity in female Wistar rats may be attributed to its antioxidant properties.

Protective Effects of Bromelain against Cadmium-Induced Pulmonary Intoxication in Rats: A Histopathologic and Cytologic Study.

Bromelain is the active substance of pineapple with a variety of therapeutic properties. In this study, the possible protective effects of bromelain were assessed against cadmium acute intratracheal exposure and its bronchopulmonary cytologic and histopathologic consequences. For this purpose, the following treatments were performed on 11 groups of Wistar rats: group 1 was negative control; groups2 and 3 received Cadmium Chloride (CdCl2) 400 µg/rat intratracheally and sampled after 5 and 10 days, respectively; groups4 and 5received bromelain 20 mg/kg orally (PO) from 14 days before until 5 and 10 days after CdCl2 instillation, respectively; groups6 and 7received bromelain 40 mg/kg from 14 days before until 5 and 10 days after CdCl2 instillation, respectively; group 8received bromelain 40 mg/kg for 24 days; groups9 and 10: celecoxib 25 mg/kg PO from 1day before until 5 and 10 days after CdCl2 instillation, respectively; group 11 received celecoxib for 11 days. Cytologic evaluation of bronchoalveolar lavage fluid revealed that intratracheal cadmium administration resulted in a significant rise in total cell count, epithelial cells, neutrophils, and eosinophils, 5- and 10-days post-exposure. Treatment with bromelain either in low or high doses in cadmium-exposed rats resulted in a significant reduction of neutrophil count. Bromelain treatment could not completely prevent or recover interstitial pneumonia and fibrinous bronchopneumonia in cadmium exposed rats. However, administration of low doses resulted in a significant decrease of semi quantitative histopathologic scores, including pneumonia and cellular infiltration indices. In conclusion, bromelain may help to improve the cytological and histopathological complications following cadmium intoxication in the lungs.

Evaluation of Blood Oxidant/Antioxidant Changes and Testicular Toxicity after Subacute Exposure to Cadmium in Albino Rats: Therapeutic Effect of Nigella sativa Seed Extracts.

AIM AND OBJECTIVE: Cells and tissues of the body are prone to oxidative damage as a result of an increased level of reactive oxygen species and nitrogen radical beyond the detoxifying ability of the endogenous antioxidant system. This study aimed to evaluate the ameliorative effect of methanolic extracts of Nigella sativa (MENS) against cadmium-induced blood oxidative stress and testicular toxicity in albino rats. MATERIALS AND METHODS: Twenty-five (25) male albino rats, weighing (200 ± 20g), were randomly grouped into five groups (A-E). Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5 mg/kg) only, group C received CdCl2 and low dose MENS (300 mg/kg, oral), group D received CdCl2 and high dose MENS (600 mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200 mg/kg, oral), for 14 days. No treatment was administered to group A (Normal control). The oxidative state of the blood was assessed by measuring the blood levels or activities of MDA, CAT, GSH and SOD; while testicular injury was assessed by measuring serum testosterone level using ELISA. The testes were harvested for histopathological examination. RESULTS: The results showed that cadmium induced a marked elevation in the level of MDA, and a decrease in SOD, CAT and GSH levels or activities (p<0.05 or p<0.01); but no significant alteration in the serum testosterone level was found (p>0.05); Histopathological studies on the testes showed that cadmium significantly induced testicular injury, which was however ameliorated by the seed extract of N. sativa. CONCLUSION: We conclude that N. sativa seed extract is potentially testiculoprotective and attenuates oxidative stress against harmful chemical toxins such as cadmium.

Investigating the underlying mechanism of cadmium-induced plant adaptive response to genotoxic stress.

Plants as sessile organisms have developed some unique strategies to withstand environmental stress and adaptive response (AR) is one of them. In the present study Cadmium (Cd)-induced AR was evaluated to ameliorate the genotoxicity of a known chemical mutagen ethyl methanesulphonate (EMS) based on cytotoxicity, genotoxicity and oxidative stress in two model plant systems Allium cepa L. and Vicia faba L. Priming the plants with cadmium chloride (CdCl2, 25 and 50 µM) reduced the genotoxicity of EMS (0.25 mM). Cd-induced AR was evident by the magnitude of adaptive response (MAR) values calculated for cytotoxicity, genotoxicity and biochemical parameters. In addition the involvement of some major metabolic pathways and epigenetic modifications in AR was investigated. Metabolic blockers of protein kinase cascades, DNA repair, oxidative stress and de novo translation interfered with the adaptive response implying their role in AR whereas, inhibitors involved in post-replication repair and autophagy were ineffective implicating that they probably have no role in the AR studied. Moreover to find the role of DNA methylation in AR, methylation-sensitive comet assay was carried out. Simultaneously 5-methyl- 2'-deoxycytidine (5mdC) levels were quantified by HPLC (high performance liquid chromatography). AR was eliminated in cells treated with a demethylating agent, 5-aza- 2'deoxycytidine (AZA). Results implied a contribution of DNA hypermethylation. To the best of our knowledge this is a first report correlating DNA methylation to Cd-induced adaptive response in plants undergoing genotoxic stress.