Lead Acetate-Injected Mice is an Animal Model for Extrapolation of Calcifying Response to Humans Due to Low Involvement of Bone Resorption.

Vascular calcification affects the prognosis of patients with renal failure. Bisphosphonates are regarded as candidate anti-calcifying drugs because of their inhibitory effects on both calcium-phosphate aggregation and bone resorption. However, calcification in well-known rodent models is dependent upon bone resorption accompanied by excessive bone turnover, making it difficult to estimate accurately the anti-calcifying potential of drugs. Therefore, models with low bone resorption are required to extrapolate anti-calcifying effects to humans. Three bisphosphonates (etidronate, alendronate, and FYB-931) were characterised for their inhibitory effects on bone resorption in vivo and calcium-phosphate aggregation estimated by calciprotein particle formation in vitro. Then, their effects were examined using two models inducing ectopic calcification: the site where lead acetate was subcutaneously injected into mice and the transplanted, aorta obtained from a donor rat. The inhibitory effects of bisphosphonates on bone resorption and calcium-phosphate aggregation were alendronate > FYB-931 > etidronate and FYB-931 > alendronate = etidronate, respectively. In the lead acetate-induced model, calcification was most potently suppressed by FYB-931, followed by alendronate and etidronate. In the aorta-transplanted model, only FYB-931 suppressed calcification at a high dose. In both the models, no correlation was observed between calcification and bone resorption marker, tartrate-resistant acid phosphatase (TRACP). Results from the lead acetate-induced model showed that inhibitory potency against calcium-phosphate aggregation contributed to calcification inhibition. The two calcification models, especially the lead acetate-induced model, may be ideal for the extrapolation of calcifying response to humans because of calcium-phosphate aggregation rather than bone resorption as its mechanism.

Sinapic acid protects against lead acetate-induced lung toxicity by reducing oxidative stress, apoptosis, inflammation, and endoplasmic reticulum stress damage.

Lead acetate (PbAc) is a compound that produces toxicity in many tissues after exposure. Sinapic acid (SNP) possesses many biological and pharmacological properties. This study aimed to investigate the efficacy of SNP on the toxicity of PbAc in lung tissue. PbAc was administered orally at 30 mg/kg and SNP at 5 or 10 mg/kg for 7 days. Biochemical, genetic, and histological methods were used to investigate inflammatory, apoptotic, endoplasmic reticulum stress, and oxidative stress damage levels in lung tissue. SNP administration induced PbAc-reduced antioxidant (GSH, SOD, CAT, and GPx) and expression of HO-1 in lung tissue. It also reduced MDA, induced by PbAc, and thus alleviated oxidative stress. SNP decreased the inflammatory markers NF-κB, TNF-α and IL-1ß levels induced by PbAc in lung tissue and exhibited anti-inflammatory effect. PbAc increased apoptotic Bax, Apaf-1, and Caspase-3 mRNA transcription levels and decreased anti-apoptotic Bcl-2 in lung tissues. SNP decreased apoptotic damage by reversing this situation. On the other hand, SNP regulated these markers and brought them closer to the levels of the control group. PbAc caused prolonged ER stress by increasing the levels of ATF6, PERK, IRE1α, GRP78 and this activity was stopped and tended to retreat with SNP. After evaluating all the data, While PbAc caused toxic damage in lung tissue, SNP showed a protective effect by reducing this damage.

Annona squamosa Fruit Extract Ameliorates Lead Acetate-Induced Testicular Injury by Modulating JAK-1/STAT-3/SOCS-1 Signaling in Male Rats.

Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. Annona squamosa fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with A. squamosa fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD50 of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD50); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD50 of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats.

Ginkgo biloba modulates ET-I/NO signalling in Lead Acetate induced rat model of endothelial dysfunction: Involvement of oxido-inflammatory mediators.

This study investigated the modulatory effect of Ginkgo biloba extract on lead acetate-induced endothelial dysfunction. Animals were administered GBE (50 mg/kg and 100 mg/kg orally) after exposures to lead acetate (25 mg/kg orally) for 14 days. Aorta was harvested after euthanasia, the tissue was homogenised, and supernatants were decanted after centrifuging. Oxidative, nitrergic, inflammatory, and anti-apoptotic markers were assayed using standard biochemical procedure, ELISA, and immunohistochemistry, respectively. GBE reduced lead-induced oxidative stress by increasing SOD, GSH, and CAT as well as reducing MDA levels in endothelium. Pro-inflammatory cytokines (TNF-α and IL-6) were reduced while increasing Bcl-2 protein expression. GBE lowered endothelin-I and raised nitrite levels. Histological changes caused by lead acetate were normalised by GBE. Our findings suggest that Ginkgo biloba extract restored endothelin-I and nitric oxide functions by increasing Bcl-2 protein expression and reducing oxido-inflammatory stress in endothelium.

A biochemical and histology experimental approach to investigate the adverse effect of chronic lead acetate and dietary furan on rat lungs.

Despite lead widespread environmental pollution, its effect on humans and livestock's respiratory systems remains inadequately investigated. Similarly, furan is industrially relevant with enormous environmental presence. Lead and furan can be ingested -via lead pipes contaminated water and heat-treated food respectively. Thus, humans are inadvertently exposed continuously. Lead toxicity is well studied, and furan have earned a position on the IARC's list of carcinogens. Here, we evaluate the effect of co-exposure to lead and furan on rat lungs. Thirty Wistar rats were grouped randomly into six cohorts (n = 6) consisting of a control group, furan alone group, lead acetate (PbAc) alone group and three other groups co-exposure to graded PbAc (1, 10 & 100 µg/L) alongside a constant furan (8 mg/kg) dose. After twenty-eight days, enzymatic and non-enzymatic antioxidant, oxidative stress and inflammatory biomarkers were biochemically evaluated. The ELISA-based technique was used to measure oxidative-DNA damage (8-OHG), tumour protein 53 (TP53) expressed and tumour necrotic factor-alpha (TNF-α) level. Dose-dependent increases (p < 0.05) in reactive oxygen and nitrogen species, malondialdehyde, nitric oxide, myeloperoxidase, TNF-α and TP53 level, with an associated decrease (p < 0.05) in enzymatic and non-enzymatic antioxidants were observed in the furan, PbAc and the co-treated rats relative to the control. In addition, PbAc and furan treatment impaired the histoarchitectural structures of rat lungs, exemplified by pro-inflammatory cell infiltration and trafficking into the bronchioles and alveolar spaces. Co-exposure to furan and PbAc may contribute to lung dysfunction via loss of redox balance, genomic damage/instability, inflammation and disrupted histoarchitectural features.

Naringenin alleviate reproductive toxicity evoked by lead acetate via attenuation of sperm profile and biochemical alterations in male Wistar rat: Involvement of TGFß/AKT/mTOR pathway.

Exposure to Lead -causes testicular dysfunction through oxidative stress, inflammation, and apoptosis; however, naringenin (NGN) therapeutic impact against lead-evoked testicular dysfunction remains elusive. Herein, the point of the study was to examine the defensive impact of NGN on testicular dysfunction initiated by lead. Seventy-Two male Wistar rats were allotted into nine groups; control group, drug control groups, lead acetate group, as well as NGN treated groups (10, 25, and 50 mg/kg) respectively, given 5 days before lead acetate treatment. The result showed clearly the impact of lead on reduced sperm count, sperm motility as well as serum testosterone and LH levels. Additionally, it caused a significant rise in testicular inflammatory markers TNF-α, IL-1ß, and TGFß, effects that were accompanied by a reduction of AKT and mTOR levels. Lead acetate also caused degenerative changes in the testis, atrophy, and loss of spermatogenic series. Our findings revealed that NGN in a dose-dependent manner improved spermiotoxicity induced by lead acetate via restoration of the testicular function, preservation of spermatogenesis, halting inflammatory cytokines along with the enhancement of germ cell survival using upregulation of AKT/mTOR expressions. The present study discloses that NGN suppresses lead acetate toxicity that is involved in the antioxidant effect in a dose-dependent manner, besides its anti-inflammatory property.

Lead acetate induces cartilage defects and bone loss in zebrafish embryos by disrupting the GH/IGF-1 axis.

Skeletal system toxicity due to lead exposure has attracted extensive attention in recent years, but few studies focus on the skeletal toxicity of lead in the early life stages of zebrafish. The endocrine system, especially the GH/IGF-1 axis, plays an important role in bone development and bone health of zebrafish in the early life. In the present study, we investigated whether lead acetate (PbAc) affected the GH/IGF-1 axis, thereby causing skeletal toxicity in zebrafish embryos. Zebrafish embryos were exposed to lead PbAc between 2 and 120 h post fertilization (hpf). At 120 hpf, we measured developmental indices, such as survival, deformity, heart rate, and body length, and assessed skeletal development by Alcian Blue and Alizarin Red staining and the expression levels of bone-related genes. The levels of GH and IGF-1 and the expression levels of GH/IGF-1 axis-related genes were also detected. Our data showed that the LC50 of PbAc for 120 h was 41 mg/L. Compared with the control group (0 mg/L PbAc), after PbAc exposure, the deformity rate increased, the heart rate decreased, and the body length was shortened at various time periods, in the 20-mg/L group at 120 hpf, the deformity rate increased by 50 fold, the heart rate decreased by 34%, and the body length shortened by 17%. PbAc altered cartilage structures and exacerbated bone loss in zebrafish embryos; in addition, PbAc exposure down-regulated the expression of chondrocyte (sox9a, sox9b), osteoblast (bmp2, runx2) and bone mineralization-related genes (sparc, bglap), and up-regulated the expression of osteoclast marker genes (rankl, mcsf). The GH level increased and the IGF-1 level declined significantly. The GH/IGF-1 axis related genes (ghra, ghrb, igf1ra, igf1rb, igf2r, igfbp2a, igfbp3, igfbp5b) were all decreased. These results suggested that PbAc inhibited the differentiation and maturation of osteoblasts and cartilage matrix, promoted the formation of osteoclasts, and ultimately induced cartilage defects and bone loss by disrupting the GH/IGF-1 axis.

Effects of sinapic acid on lead acetate-induced oxidative stress, apoptosis and inflammation in testicular tissue.

In this study, the effect of lead acetate (PbAc) and sinapic acid (SNP) administration on oxidative stress, apoptosis, inflammation, sperm quality and histopathology in testicular tissue of rats was tried to be determined. PbAc was administered at a dose of 30 mg/kg/bw for 7 days to induce testicular toxicity in rats. Oral doses of 5 and 10 mg/kg/bw SNP were administered to rats for 7 days after PbAc administration. According to our findings, while PbAc administration increased MDA content in rats, it decreased GPx, SOD, CAT activity and GSH content. NF-kB, IL-1ß, TNF-α, and COX-2, which are among the inflammation parameters that increased due to PbAc, decreased with the administration of SNP. Nrf2, HO-1, and NQO1 mRNA transcript levels decreased with PbAc, but SNP treatments increased these mRNA levels in a dose-dependent manner. RAGE and NLRP3 gene expression were upregulated in PbAc treated rats. MAPK14, MAPK15, and JNK relative mRNA levels decreased with SNP treatment in PbAc treated rats. While the levels of apoptosis markers Bax, Caspase-3, and Apaf-1 increased in rats treated with PbAc, the level of Bcl-2 decreased, but SNP inhibited this apoptosis markers. PbAc caused histopathological deterioration in testis tissue and negatively affected spermatogenesis. When the sperm quality was examined, the decrease in sperm motility and spermatozoon density caused by PbAc, and the increase in the ratio of dead and abnormal spermatozoa were inhibited by SNP. As a result, while PbAc increased apoptosis and inflammation by inducing oxidative stress in testicles, SNP treatment inhibited these changes and increased sperm quality.

Naphthaleneoxypropargyl-Containing Piperazine as a Regulator of Effector Immune Cell Populations upon an Aseptic Inflammation.

This study investigated the effects of aseptic inflammation and heavy metal exposure on immune responses, as well as the potential immunomodulatory properties of the newly synthesized 1-[1-(2,5-dimethoxyphenyl)-4-(naphthalene-1-yloxy)but-2-ynyl]-4-methylpiperazine complexed with ß-cyclodextrin (ß-CD). Aseptic inflammation was induced by a subcutaneous injection of turpentine in rats, while heavy metal exposure was achieved through a daily administration of cadmium chloride and lead acetate. The levels of immune cell populations, including cytotoxic T lymphocytes (CTL), monocytes, and granulocytes, were assessed in the spleen. The results showed that aseptic inflammation led to decreased levels of CTL, monocytes, and granulocytes on the 14th day, indicating an inflammatory response accompanied by a migration of effector cells to the inflamed tissues. The exposure to cadmium chloride and lead acetate resulted in systemic immunotoxic effects, with reduced levels of B cells, CD4+ Th cells, monocytes, and granulocytes in the spleen. Notably, piperazine complexed with ß-CD (the complex) exhibited significant stimulatory effects on CD4+, CD8+, and myeloid cell populations during aseptic inflammation, even in the presence of heavy metal exposure. These findings suggest the potential immunomodulatory properties of the complex in the context of aseptic inflammation and heavy metal exposure.

Cabbage juice supplementation abrogates Lead acetate-induced haematological and haemorheological imbalances in male Wistar rat.

Lead is a hazardous naturally found heavy metal that has been reported to induce haematological alterations. Whether cabbage, a commonly consumed vegetable rich in antioxidants and anticancer compounds, can mitigate these alterations remains unknown. This study investigated the protective effect of cabbage juice against Lead-induced haematological changes. Twenty (20) male Wistar rats were randomly selected into four groups (n = 5) and given distilled water (1 ml/100 g b.wt), Lead acetate (25 mg/kg b.wt), Cabbage juice (1 ml/100 g b.wt), and Lead acetate with Cabbage juice. All treatments were given orally for 28 days. Lead exposure induces normocytic normochromic anemia with substantial leukocytosis, lymphocytopenia, and hyperfibrinogenemia. Lead-intoxicated animals had significantly higher haemolysis and prolonged clotting times. However, cabbage juice reverses these adverse haematological and haemorheological changes induced by Lead acetate. Conclusively, cabbage juice demonstrated antioxidant, anti-inflammatory, anti-thrombotic, and immunomodulatory properties, as well as the ability to protect the red blood cell membrane from damage caused by Lead-induced osmotic stress.

L-Ascorbic Acid and Curcumin Prevents Brain Damage Induced via Lead Acetate in Rats: Possible Mechanisms.

Lead acetate (lead ac.) is a widespread ecological toxicant that can cause marked neurotoxicity and decline in brain functions. This study aimed to evaluate the possible neuroprotective role of L-ascorbic acid (ASCR) and curcumin (CRCM) alone or together against lead ac.-induced neurotoxicity. Rats were injected with lead ac. then treated orally with ASCR and CRCM alone or in combination for 7 days. Lead ac. caused elevation in brain tumor necrosis factor-α, interleukin-6, caspase-3, and malondialdehyde levels, while superoxide dismutase, reduced glutathione as well as the expression of brain-derived neurotrophic factor, cAMP response element-binding, and Beclin1 were downregulated. Expressions of C/EBP homologous protein and mammalian Target of rapamycin kinase were upregulated in brain tissues matched with the control group. Histopathological examination supported the previously mentioned parameters, the administration of the antioxidants in question modulated all the altered previous parameters. The combination regimen achieved the superlative results in the antagonizing lead ac.-induced neurotoxicity via its antioxidant and antiapoptotic activities.

Cabbage juice protect against lead-induced liver and kidney damage in male Wistar rat.

AIM: Liver and kidney has been implicated in Lead toxicity and this has been linked to oxidative damage. On the other hand, cabbage is one of the widely consumed vegetables with a plethora of health benefits. This present study investigated the protective effect of cabbage juice on lead-induced toxicity in male Wistar rats. METHODS: Twenty male Wistar rats were randomly divided into four groups (n = 5) and were treated with distilled water (1 ml/100 g b.wt), Lead acetate (25 mg/kg b.wt), cabbage juice (1 ml/100 g b.wt) and Lead acetate plus cabbage juice respectively. All treatments were administered orally for 28 days. Following euthanasia, blood was collected and serum decanted for biochemical assay and liver and kidney tissues were harvested, prepared for antioxidant activity and histological study. RESULT: Cabbage juice significantly attenuated Lead-induced liver and kidney dysfunction by lowering serum concentrations of urea, creatinine, ALP, AST and ALT. Antioxidants (SOD, CAT, GSH) were also upregulated in liver and kidney tissues. Cabbage juice restored the histoarchitectural changes caused by lead intoxication. CONCLUSION: Cabbage juice consumption protected the liver and kidney against lead-induced toxicity by enhancing in vivo anti-oxidant defense system.

Selenium nanoparticles alleviate lead acetate-induced toxicological and morphological changes in rat testes through modulation of calmodulin-related genes expression.

Lead (Pb) is one of the most common toxic heavy metals. It is a well-known testicular toxicant. Selenium nanoparticles (SeNPs) are a more effective form of elemental selenium that reduces drug-induced toxicities. This study aimed to study the possible ameliorating effect of SeNPs on the toxicological and morphological changes in testes of lead acetate intoxicated rats. The study was conducted on 40 adult male albino rats divided into four groups; control, SeNPs-treated, lead acetate-treated, lead acetate and SeNPS treated groups. The concurrent treatment of lead acetate-exposed rats with SeNPs (0.1 mg/kg/day) for 12 weeks significantly lowered the blood and testicular lead levels, increased serum testosterone, and decreased luteinizing hormone and follicle-stimulating hormone to approach control values. In addition, it improved the histopathological, and ultrastructural alterations of the testes and improved the immunohistochemical expression of the c-kit. This was accompanied by maintenance of the testicular oxidant/antioxidant balance and reversing the lead-induced disrupted calmodulin-related genes expression in testicular tissue in the form of downregulation of CAMMK2 and MAP2K6 and upregulation of CXCR4 genes. There was a strong positive correlation between testicular malondialdehyde and MAP2K6 expression level as well as a strong positive correlation between CXCR4 gene expression and the C-kit area %. In conclusion, SeNPs can be considered as a potential therapy for a lead-induced testicular injury.

Cabbage (Brassica oleracea) mitigates lead (II) acetate-induced testicular dysfunction in Wistar rats via up-regulation of Bcl-2 protein expression, pituitary-testicular hormonal axis and down-regulation of oxido-inflammatory reactions.

Oxido-inflammatory stress has been involved in lead-induced testicular dysfunction and plants rich in anti-oxidants has been reported to be beneficial in combating heavy metal poisonings in animal studies. However, cabbage juice protective effect on lead-induced testicular dysfunction was investigated in this study. Twenty male Wistar rats were selected into four (n = 5) groups and given distilled water (1 ml/100 g body weight), lead acetate (25 mg/kg body weight), cabbage juice (1 ml/100 g body weight), and lead acetate with cabbage juice, respectively. All treatments were administered orally for 28 days. Sperm count, motility, viability, testosterone, luteinising hormone and follicle-stimulating hormone, testicular Bcl-2 expression, and enzymatic anti-oxidant capabilities were considerably (p < 0.05) decrease in lead-treated animals. However, cabbage juice significantly (p < 0.05) elevated these parameters. Testicular malondialdehyde, tumour necrosis factor-α, nitric oxide and interleukin-6 was elevated by lead acetate. When comparing cabbage juice-treated animals to lead-treated animals, all of these parameters were considerably (p < 0.05) downregulated in cabbage juice-treated animals. Following lead administration, the testes' histomorphological alterations were not totally recovered despite therapy with cabbage juice. Conclusively, this study suggest that cabbage juice mitigates testicular dysfunction associated with lead exposure via its anti-oxidant, anti-inflammatory, anti-apoptotic and androgenic properties.

Dose and time response study to develop retinal degenerative model of zebrafish with lead acetate.

Objective: Animal models are the silent scouts that help to understand the complex biological processes and gather data that aid our understanding of how organisms function. Various animal models are being sacrificed to assess the impact of toxic chemicals. Mortality calculations should be minimised and much data should be collected on the basis of clinical signs that can contribute to identifying robust humane endpoints linked to mortality. This study was designed to calculate the lowest possible dose of PbAc (lead acetate), a neurotoxicant, that can have a toxicological impact on the zebrafish retina and to minimise animal usage. Dose and time-dependent changes were observed in the zebrafish retina following PbAc exposure with zero mortality. Vision and visual behaviour response are the foremost indicators that can be recorded to mark the risk assessment of any chemical. Therefore, the present study aims at dose and time response to find the lowest dose of PbAc affecting the zebrafish retina and its visual behaviour.Materials and methods: Zebrafish were treated for 3 weeks with four concentrations of 0.04, 0.06, 0.08, and 0.1 mg/L of PbAc for a dose-response study. Then for the time response study, two doses 0.08 and 0.1 mg/L were selected and zebrafish were exposed to those concentrations for 2 and 4 weeks.Results: The results of qualitative and quantitative analyses of retinal histology showed that 15 days of treatment with 0.08 mg/L concentration can cause appropriate damage to the photoreceptor layer. At the ultrastructural level, it was further observed that PbAc induces damage to the photoreceptors, especially the rod cells. Escape response sbehaviour showed a significant decrease in visual response to changing contrasts in an increasing dose-dependent manner.Conclusion: In conclusion, it has been shown that 15 days treatment with 0.08 mg/L lead acetate induce retinal degeneration in zebrafish without causing any mortality.

Analysis of the Mechanisms of Impairment of Functional Parameters of Internal Organs in Saturnism in an Experiment in Rats.

In rats with lead intoxication (intramuscular administration of lead acetate in a dose 5 mg/kg for 30 days), the development of oxidative stress, reduced expression of endothelial NO synthase and total metabolites of NO production, as well as an increased content of norepinephrine were observed. Lead-induced nephropathy developed; diuresis and sodium excretion increased due to a decrease in tubular transport of water and sodium ions. Activation of free-radical reactions in cells of the renal cortex and medulla contributed to inhibition of Na,K-ATPase. LPO caused damage to cardiomyocytes, hepatocytes, which was seen from elevation of AST, ALT, γ-glutamyl transpeptidase, and alkaline phosphatase in the blood serum and a decrease in activity of Na,K-ATPase in the organs tissues. Metabolic disorders revealed in saturnism in experimental rats (LPO activation, reduced expression of endothelial NO synthase and total metabolites of NO, and increased blood norepinephrine) contributed to the development of vascular endothelial dysfunction and hemodynamics disturbances, and damage to cells of internal organs: kidney, myocardium, liver.

[Mechanism of paeoniflorin inhibiting apoptosis of hippocampal neurons of rats induced by lead acetate].

Objective: To investigate the effect and underlying mechanism of paeoniflorin on hippocampal neuron apoptosis induced by lead acetate. Methods: In September 2020, primary hippocampal neuronal cells were isolated and cultured from fetal rats, and identified using cellular immunofluorescent. MTT assay was used to measure the cell viability to determine the concentration and time of lead acetate-induced hippocampal neuron apoptosis. MTT was also used to evaluate the effect of paeoniflorin concentration on the apoptosis of hippocampal neurons induced by lead acetate. According to the results, different concentrations of paeoniflorin were selected to intervene hippocampal neuron cells, after 24 h, lead acetate was added to the cells, meanwhile, blank and model groups were set up, the content of reactive oxygen species (ROS) , superoxide dismutase (SOD) , lactate dehydrogenase (LDH) , malondialdehyde (MDA) and Caspase-3 were measured. Extracellular signal regulated kinase (ERK) , phosphorylated ERK (p-ERK) , p38 mitogen -activated protein kinases (p38MAPK) , phosphorylated p38MAPK (p-p38MAPK) , c-Jun N-terminal kinase (JNK) and phosphorylated JNK (p-JNK) protein expression in hippocampal neuronal cells were determined by Western blotting. Results: The isolated and cultured hippocampal neurons were identified by immunofluorescence chemical staining and then treated with lead acetate, MTT results showed that lead acetate had the best toxicity effect when treated for 24 h at a concentration of 25 µmol/L. Paeoniflorin showed no cytotoxic effect on hippocampal neuronal cells when the concentrations below 80 µmol/L. Compared with the model group, the activity of hippocampal neuronal cells was significantly increased after treating with 20, 40 or 80 µmol/L paeoniflorin (P<0.05) . Compared with the blank group, the ROS activity, LDH release level, MDA content and caspase-3 content were significantly increased (P<0.01) , and the SOD activity was significantly decreased (P< 0.01) in the hippocampal neuronal cells of the model group. Compared with the model group, the ROS activity, LDH release level, MDA content and caspase-3 content were obviously decreased (P<0.05) , SOD activity was significantly increased (P <0.01) after hippocampal neuronal cells were treated with 40 or 80 µmol/L paeoniflorin. Relative to the model group, the ratio of p-ERK/ERK were significantly up-regulated (P<0.01) , while the ratios of p-p38MAPK/p38MAPK and p-JNK/JNK were significantly down-regulated after hippocampal neuronal cells were treated with 40 or 80 µmol/L paeoniflorin (P<0.05) . Conclusion: Paeoniflorin may down-regulate the expression of p-p38MAPK and p-JNK protein, up-regulate the expression of p-ERK protein, and inhibit the apoptosis of hippocampal neurons induced by lead acetate through the MAPK signaling pathway.

Correlation between urinary KIM-1 and kidney protein expression of p-ERK following damage in rats exposed to gentamicin or lead acetate.

Kidney injury molecule-1 (KIM-1) is a membrane receptor upregulated in the proximal tubule cells following various types of kidney injuries. Notably, studies have suggested a correlation between KIM-1 expression and extracellular signal-regulated kinase (ERK) activation. In this study, we aimed to investigate the association between the kidney overexpression pattern of cytoplasmic phosphorylated-ERK (p-ERK) protein and increased urinary KIM-1 levels in rats exposed to gentamicin or lead acetate, both at the end of toxic exposure and after a 4-week recovery period. Although other proteins were evaluated, only kidney overexpression of cytoplasmic p-ERK protein correlated with increased urinary KIM-1 levels. For both toxic substances, the increased urinary KIM-1 levels corresponded with kidney inflammation. Our results suggest that KIM-1 and p-ERK share a common mechanism in kidney injury mediated by both toxic substances that induce proximal tubule damage.

Anthocyanin from purple sweet potato attenuates lead-induced reproductive toxicity mediated by JNK signaling pathway in male mice.

The present work aimed to explore the protective effect of APSP on Pb-induced reproductive toxicity and possible mechanism. APSP (100 mg/kg) was administered to Pb-intoxicated (0.2% lead acetate) male Kunming mice once daily by oral gavage for 6 weeks. Our results showed that APSP exerted male reproductive protection effects as showed by attenuated Pb-induced testicular injury, improved sperm count and motility, and reduced sperm abnormality rate. APSP also restored Pb-induced decrease in both enzymatic and non-enzymatic antioxidants, and GSH/GSSG ratio, but inhibited lipid peroxidation in serum and testes. Moreover, APSP downregulated Pb-induced Bax mRNA and protein expressions, suppressed activation of caspase-3, upregulated Bcl-2 protein expression, and prevented Pb-induced DNA damage. APSP treatment also interfered with Pb-induced testicular JNK signaling through inhibition of JNK mRNA expression and phosphorylation, resulting in inhibition of c-Jun expression. These effects of APSP were abolished by Pb. In conclusion, APSP represents a potential therapeutic agent for preventing Pb-caused reproductive toxicity, which is attributed to its antioxidant and anti-apoptotic properties, as well as, modulation of JNK signaling pathway.

Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K/AKT Signaling Pathway.

Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg/kg body weight (b.w.)/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg/kg b.w./day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg/kg b.w./day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman-Keul's test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K/AKT signaling pathways.