Injection Of Cadmium Chloride Research Articles

Protective Effects of Annona Atemoya Extracts on Inflammation, Oxidative Stress, and Renal Function in Cadmium-Induced Nephrotoxicity in Wistar Rats.

Cadmium (Cd), a highly toxic heavy metal from agricultural activities, and its exposure can lead to impaired renal function by increasing reactive oxygen species. The atemoya fruit is known for its high phenolic and antioxidant compounds. This study aimed to evaluate the effects of atemoya extracts on renal function, oxidative stress parameters, and inflammatory biomarkers in a cadmium-induced nephrotoxicity model. Three aqueous extracts were prepared from different parts of the atemoya fruit: seeds, peel, and pulp. Twenty-five male Wistar rats were allocated into four groups: control, seed, peel, and pulp extracts at 2 g/kg for 25 days. All treatment groups administered intraperitoneal injections of cadmium chloride (CdCl2) (2 mg/kg) to induce renal damage. The cadmium-treated groups showed decreased creatinine clearance, SOD, CAT, and GPx activities (p < 0.05) and increased serum levels of TNF-α and IL-6 compared to the control group (p < 0.05). The treatment with seed, peel, and pulp extracts increased creatinine clearance (p < 0.05), increased SOD, CAT, and GPx activities (p < 0.05), and reduced serum levels of TNF-α and IL-6 compared to the Cd group (p < 0.05). This study supports the use of atemoya as a promising candidate for mitigating nephrotoxicity and highlights the importance of its antioxidant and anti-inflammatory properties in renal health.

The melatonin receptor agonist agomelatine protects against acute pancreatitis induced by cadmium by attenuating inflammation and oxidative stress and modulating Nrf2/HO-1 pathway

Pancreatitis is a serious effect of the heavy metal cadmium (Cd) and inflammation and oxidative stress (OS) are implicated in Cd-induced pancreatic injury. This study evaluated the effect of the melatonin receptor agonist agomelatine (AGM) on Cd-induced acute pancreatitis (AP), pointing to its modulatory effect on inflammation, OS, and Nrf2/HO-1 pathway. Rats were supplemented with AGM orally for 14 days and a single injection of cadmium chloride (CdCl2) on day 7. Cd increased serum amylase and lipase and caused pancreatic endocrine and exocrine tissue injury. Malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) were elevated, nuclear factor (NF)-kB p65, inducible NO synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-α and CD40 were upregulated, and antioxidants were decreased in the pancreas of Cd-administered rats. AGM ameliorated serum amylase and lipase and pancreatic OS, NF-kB p65, CD40, pro-inflammatory mediators and caspase-3, prevented tissue injury and enhanced antioxidants. AGM downregulated Keap1 and enhanced Nrf2 and HO-1 in the pancreas of Cd-administered rats. In silico findings revealed the binding affinity of AGM with Keap1, HO-1, CD40L and caspase-3. In conclusion, AGM protected against AP induced by Cd by preventing inflammation, OS and apoptosis and modulating Nrf2/HO-1 pathway.

Cadmium exposure induces pyroptosis in testicular tissue by increasing oxidative stress and activating the AIM2 inflammasome pathway

High doses of cadmium (Cd) cause irreversible injury to the reproductive system, especially testicular tissue. Studies have shown that pyroptosis is involved in Cd-induced tissue damage, but whether pyroptosis is involved in damage to testicular tissue following Cd exposure remains unclear. To investigate the mechanism of pyroptosis in testicular injury induced by Cd exposure, we used 8-week-old male C57BL/6J mice subjected to consecutive 7 days of intraperitoneal injection of cadmium chloride (CdCl2) at concentrations of 0, 1.0 and 3.0 mg/kg. The results indicated that 3.0 mg/kg CdCl2 significantly decreased serum testosterone levels, sperm concentration and sperm motility, while increased LDH and IL-1β levels. Testicular HE staining indicated that Cd exposure damaged the interstitial cells and increased the atypical residual bodies. Fluorescence results indicated that 3.0 mg/kg CdCl2 increased ROS levels, DNA damage, and the number of TUNEL-positive seminiferous tubule cells in testicular tissue. Transcriptome analysis showed that Cd exposure mainly induced inflammatory and chemokine signaling pathways in testicular tissue, with upregulated mRNA levels of Aim2, and reduced mRNA levels of Nlrp3. Further analysis showed that 3.0 mg/kg CdCl2 increased the expression of testicular HO-1, SOD2, γH2AX and PARP-1, as well as the pyroptosis-related factors GSDMD, GSDME, Caspase-1, ASC and IL-1β. In conclusion, our results provide a possible mechanism by which Cd exposure activates the AIM2 pathway by increasing oxidative stress injury to induce pyroptosis in testicular tissue. This provides a new perspective on testicular damage caused by Cd exposure.

Comparative study on the effect of cadmium and hydrocortisone treatment on the brain of rats experimentally infected with Toxoplasma gondii

This study was dedicated to detecting the effects of cadmium chloride and of cortisone on experimental infection with Toxoplasma gondii in rats through studying brain tissue. Twenty-four adult albino male rats were used, divided into four groups, comprising: untreated control as group 1, group 2: infected with intraperitoneal injection of Toxoplasma gondii 80 tissue cysts per animal, group 3: infected with Toxoplasma gondii and treated with intraperitoneal injection of cadmium chloride 1.5mg/kg once a week, group 4: infected with Toxoplasma gondii and treated with intramuscular injection of hydrocortisone in a dose 0.5 mg/kg once a week. After 30 days of treatment for all groups, the animals were sacrificed, and the gross and histopathological examinations were performed on the brains of the rats. The results revealed the presence of changes in the infected groups including appearance of toxoplasma tissue cysts in the grey matter, with mild to moderate perineuronal and periaxonal edema. There were further changes observed in infected groups which treated with cadmium chloride including perineuronal satelletosis, perineuronal edema and demyelination in neuronal axons, otherwise the infected groups treated with cortisone did not show any noticeable difference from the group of infection only. It is concluded that cadmium increase the intensity of occurrence of lesions induced by Toxoplasma gondii in the brain tissue of the rats, considering that all noticeable lesions ranged from mild to moderate in severity, and the differences between groups may be related to the nature of the pathogen used.

Protective effects of caffeic acid phenethyl ester on cadmium-induced testicular injury: A crucial role of antioxidant enzymes in male mice infertility

Infertility in men is referred to inability to achieve pregnancy in fertile females after at least one year of regular intercourse. The lack of oxygen in the environment may lead to an imbalance of testes production. Swiss mice were alienated into four groups 10 mice/each. This included one negative normal control group I. The induction of infertility was achieved with injection of cadmium chloride at dose 3 mg/kg body weight for four consecutive days for the rest groups. Group III received vehicle (saline) from the second day of induction for the similar period during the experiment. Infertile mice determined depending on alterations in morphology, motility, and reduced sperm count. Group IV was treated with 3 mg/kg of caffeic acid phenethyl ester (CAPE) per day, for 6 days from the second day of cadmium intoxication. Data showed effectiveness of CAPE significantly through improving the antioxidant enzymes SOD, GST and GSH in testes homogenate and GSH-Px in mice serum that were treated compared to those in the untreated group II (P˂0.001). The histopathology, DNA analysis showed marked improvement in spermatogenesis and DNA intact pattern in treated mice testis. Overall, the results demonstrated the ability of CAPE to improve spermatogenic cells. The data analysis indicated the possibility for the future use of CAPE as an inhibitory agent of infertility. Clinical trials and further studies are required to evaluate the definite medical effects of CAPE based on abundant experimental studies, with predictive future applications in human clinical trials.

Effect of Fucoxanthin Administration on Thyroid Gland Injury Induced by Cadmium in Mice.

The intervention effect of fucoxanthin, which is reportedly a powerful antioxidant, on cadmium-induced thyroid damage in mice was evaluated. Animals (N = 120) were divided into control group (given pure water, N = 20) and CdCl2-exposed group (given CdCl2 orally at a dose of 30 mg/kg body weight (bw)/day for 30 days, N = 100). Besides, the CdCl2-exposed group was divided into the following 5 groups (N = 20) to evaluate the intervention effect of fucoxanthin: (1) negative control group (NCG; animals were supplied with pure water); (2) positive control group (PCG; animals were supplied with 50 mg/kg bw/day thyroid tablets. Thyroid tablets are made from the thyroid glands of pigs, cattle, sheep and other food animals (the main components of T4). But because they are extracts of the thyroid glands, they may contain a small amount of T3. The specific amount of T3 is unknown.); (3) low fucoxanthin concentration group (F1; animals were supplied with 10 mg/kg bw/day fucoxanthin); (4) medium fucoxanthin concentration group (F2; animals were supplied with 25 mg/kg bw/day fucoxanthin); (5) high fucoxanthin concentration groups (F3; animals were supplied with 50 mg/kg bw/day fucoxanthin). A 14-day treatment was conducted for these animals. The levels of T4, T3, MDA, ascorbate peroxidase (APX) and catalase were measured, and the expression levels of Bax, Bcl-2, ERK1, ERK2, MEK1, eIf2α, p-eIf2α, GRP78 and GRP94 genes were determined using real-time reverse transcriptase-polymerase chain reactions (RT-PCR). In addition, tissue histopathology and ultrastructure were recorded and analysed. We found that the injection of cadmium chloride (CdCl2) decreased serum T4 and T3 levels to 27.10 ng/ml and 837.74 pg/ml, respectively. In addition, CdCl2 intoxication induced oxidative stress, structural abnormalities and apoptosis in thyroid follicles. Our results showed that the treatment of CaCl-exposed mice with 25-50 mg/kg bw/day fucoxanthin appreciably decreased oxidative stress and apoptosis induced by CdCl2 and restored the microstructural and ultrastructural organisations of the thyroid gland towards normalcy. Compared with the negative control group, fucoxanthin treatment groups showed significant increase in T4 and T3 levels (52.17 ng/ml and 1669.18 ng/ml, respectively; P < 0.05), relieved oxidative stress by decreasing malondialdehyde level and increasing catalase and APX levels and increased apoptosis inhibition through inhibiting the ERK1/2 pathway and preventing endoplasmic reticulum stress in thyroid follicular epithelial cells. Herein, our study provides evidence of the protective effects of fucoxanthin supplementation against thyroid damage and suggests therapeutic potential of this pigment in cases of Cd intoxication and hypothyroidism.

Protective effect of Polygonatum sibiricum against cadmium-induced testicular injury in mice through inhibiting oxidative stress and mitochondria-mediated apoptosis

Ethnopharmacological relevancePolygonatum sibiricum (PS), the dried rhizome of the liliaceous plant including P. sibiricum Red., P. cyrtonema Hua. and P. kingianum Coll. et Hemsl., is a widely used Chinese herbal medicines. It was first published in "Special Records of Famous Doctors", in which is described to replenished Qi and nourish Yin, strengthening the spleen and nourishing the lungs and kidney. Based on the principle of kidney controlling the reproduction, kidney-tonifying therapy has traditionally been seen as most applicable to the treatment of infertility. The current investigation has focused on the protective effect of PS against cadmium-induced testicular injury in mice. Aim of the studyTo investigate the protective effect of PS against cadmium-induced testicular injury in mice via the TXNIP-NLRP3-Caspase-1 and CytC-Caspase-9-Caspase-3 pathways. Materials and methodsPS was processed into Polygonatum sibiricum aqueous extract (PSAE). A mouse testicular injury model was established by a single intraperitoneal (i.p.) injection of cadmium chloride (CdCl2) (2.5 mg/kg b.w.), and the mice were treated intragastrically with PSAE (10 g/kg b.w.) once daily for 35 consecutive days. At the end of the experiment blood and testicular tissue samples were collected to analyze sperm survival rate and sperm deformity rate, serum testosterone T content, testicular oxidation related indicators levels (SOD, MDA, GSH, CAT) in testicular tissue, and histopathological changes of testicular tissues. The testicular cell cycle and reactive oxygen species (ROS) levels were measured by flow cytometry, the expression levels of thioredoxin-interacting protein (TXNIP), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, interleukin (IL)-1β, Cyctochrome C (CytC), Caspase-3, and Caspase-9 mRNA in testicular tissue were detected by qRT-PCR and the protein expression levels of TXNIP, NLRP3, Caspase-1, CytC, Caspase-3, and Caspase-9 were detected by Western blot and immunohistochemical method. ResultsThe results indicated that compared with the model group, PSAE brought testicular weight to a near-normal range, improved sperm survival rate and reduced sperm abnormality rate, elevated the level of testosterone, made the damaged testis tissue recover to near normal, reduced the level of ROS, and inhibited testicular cell apoptosis. Further study showed that PSAE significantly decreased the levels of relative genes and proteins in testicular cells, such as TXNIP, NLRP3, Caspase-1, IL-1β, CytC, Caspase-3, and Caspase-9, which suggested that PSAE could regulate oxidative stress through the TXNIP-NLRP3-Caspase-1 signaling pathway, and inhibit apoptosis in the mitochondrial pathway via CytC-Caspase-9-Caspase-3 pathway. In summary, we have confirmed that PSAE exerted a powerful protective effect on CdCl2-induced testicular injury in mice through inhibiting oxidative stress and mitochondria-mediated apoptosis.

Cadmium inhibits lysine acetylation and succinylation inducing testicular injury of mouse during development

The toxic effects of cadmium (Cd) in the reproductive system have been confirmed, and lysine acetylation and succinylation play important roles in spermatogenesis. However, little attention determined whether Cd could affect lysine acylation and how it might have an impact on the reproductive system. Therefore, with the goal of contributing to this subject, we have examined the effects of Cd on lysine acetylation and succinylation of proteins in the germ cells of male mice testes during different developmental stages. We adopted intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) in mice once every 5 days from postnatal day 5–60. The results showed that Cd could restrict GAPDH activity, ATP and cAMP levels of germ cells to inhibit lysine acetylation and succinylation in the testes, inducing reproductive injuries. Cd also restricts acetylation of histone H4K5 and H4K12, which could result in failure of spermiogenesis. Remarkably, polarized acetylation occurs in meiosis, and high-level acetylation occurs earlier than high-level succinylation during spermatogenesis. Moreover, Cd has a limited effect on body weight but reduces the weight of the testis and litter size. Our research may provide a new way to reveal the mechanisms of Cd reproductive toxicity related to lysine acetylation and succinylation.

Protective effect of grape or apple juices in bone tissue of rats exposed to cadmium: role of RUNX-2 and RANK/L expression.

The aim of this study was to investigate if grape or apple juices are able to protect bone tissue of rats exposed to cadmium. For this purpose, histopathological analysis and immunohistochemistry for RUNX-2 and RANK-L were investigated in this setting. A total of 20 adult Wistar rats were distributed into four groups (n = 5), as follows: control group, cadmium group, cadmium and grape juice group, and Cadmium and apple juice group. Control group received a single intraperitoneal (i.p.) water injection. Cadmium group received a single i.p. injection of cadmium chloride (1.2mg/kg body weight) diluted in water. Cadmium and grape juice and cadmium and apple juice groups received a single i.p. injection of cadmium chloride (1.2mg/kg body), and after 15days, the rats were treated with grape or apple juices for 15days, by gavage. All animals were euthanized 30days after the beginning of experiment. Histopathological analysis in rat femur revealed extensive bone loss in rats intoxicated with cadmium. Grape or apple juices were able to increase bone formation. Cadmium inhibited RUNX-2 immunoexpression whereas cadmium increased RANK-L immunoexpression in rat bone cells. Grape or apple juices increased RUNX-2 and decreased RANK-L immunoexpression after cadmium intoxication. Taken together, our results demonstrate that grape or apple juices are able to exert therapeutic activity following cadmium intoxication in rat bone tissue as result of stimulatory effect of bone formation by RUNX-2 upregulation and RANK-L downregulation.

Experimental Research on Therapeutic Efficacy of Traditional Chinese Medicine Shengjing Capsule Extracts in Treating Spermatogenesis Impairment Induced by Oxidative Stress.

BackgroundTo investigate antioxidant effects of traditional Chinese Shengjing capsule extracts (sperm-producing capsule, with functions of tonifying kidney and invigorating kidney essence) on testes, epididymides, and sperms of rats.Material/MethodsWe randomly divided 50 rats into 5 groups. G1: normal control group (treated with saline); G2: cadmium chloride group; G3: cadmium chloride+ low doses of drugs; G4: cadmium chloride + medium doses of drugs; and G5: cadmium chloride + high doses of drugs (equivalent dose: 0.45 g/kg). In addition to the normal control group, the other 4 groups started receiving intraperitoneal injection of cadmium chloride (1 mg/kg, i.p.). Testicular glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and malondialdehyde aldehyde (MDA) were measured by ELISA; epididymis histopathological examination was performed; testis serum testosterone (T) was measured; specimens of the epididymal semen were analyzed for sperm concentration, morphology, vitality, and DNA fragmentation rate.ResultsSperm count and activity of rats in the model control group decreased significantly; their MDA concentration of testicular and epididymal homogenates increased greatly; while the vitality of SOD and GSH-Px dropped sharply. All indexes mentioned above were significantly different from those of the blank control group (P<0.05); the sperm count and activity of rats treated with Shengjing capsule (sperm-producing capsule) decreased, but were still significantly higher than those of the model group (P<0.05). MDA level of rats treated with Shengjing capsule were significantly lower than that of the model group (P<0.05), while their SOD and GSH-Px activity were significantly higher than the model group (P<0.05). The normal morphology rate and DNA integrity rate of groups treated with Shengjing capsule were significantly higher than those of the model group (P<0.05).ConclusionsShengjing can enhance the activity of antioxidant enzymes and inhibit oxidative stress. It can also repair testicular and epididymal pathological damages, protect spermatogenesis, increase sperm count and activity, and improve normal morphology rate of sperm.

Increased Oxidative DNA Damage in Placenta Contributes to Cadmium-Induced Preeclamptic Conditions in Rat.

To explore the possible mechanisms of cadmium (Cd)-induced preeclamptic conditions in rats. In the present study, we introduced the in vivo model of preeclampsia by giving intraperitoneal injections of cadmium chloride (CdCl2) to pregnant rats from gestational day (GD) 4 to 19. Maternal body weights were recorded on GD 0, 14, and 20, while their systolic blood pressures (SBPs) monitored on GD 3, 11, and 18. On GD 20, rats were sacrificed and the specimens were collected. The morphological changes of placenta and kidney tissues of pregnant rats were examined by hematoxylin and eosin staining assay. Blood Cd level was detected by inductively coupled plasma mass spectrometry. Total antioxidant capacity (TAC) was evaluated using FRAP method and total nitrite (NOx) was detected with Griess reagent. Antioxidative factors and DNA damage/repair biomarkers were measured by real-time qPCR, western blot or immunohistochemistry study. The current results showed that CdCl2-treated pregnant rats developed preeclampsia (PE)-like manifestations, such as hypertension, albuminuria, with decreased TAC and increased blood Cd level, and pro-oxidative/antioxidative or DNA damage/repair biomarkers. Our study demonstrated that increased oxidative DNA damage in placenta could contribute to Cd-induced preeclamptic conditions in rat.

Antimutagenic and antigenotoxic potential of grape juice concentrate in blood and liver of rats exposed to cadmium.

The aim of this study was to evaluate the antimutagenic and antigenotoxic potential of grape juice concentrate in rodent organs exposed to cadmium chloride intoxication. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (CTRL; nontreated group), cadmium group (Cd), and cadmium-grape juice group (Cd + GJ). Exposed animals received intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) diluted in water and, after 15 days, Cd + GJ group received grape juice concentrate for 15 days, by gavage (0.8 mL, 1.18 mg of polyphenols kg(-1) day(-1)). Grape juice concentrate was able to decrease genotoxic effects induced by cadmium in peripheral blood and liver cells as depicted by single cell gel (comet) and micronucleus assays. A decrease for anti-8-hydroxy-20-deoxyguanosine (8OHdG) expression in hepatocytes of animals exposed to cadmium and treated with grape juice concentrate was also detected. Higher CuZn-SOD activity was observed in liver cells of the Cd + GJ group. No remarkable differences were seen regarding Mn-SOD activity among groups. Taken together, our results demonstrate that grape juice concentrate was able to exert antimutagenic and antigenotoxic activities in blood and liver cells of rats exposed to cadmium.

Thymoquinone therapy abrogates toxic effect of cadmium on rat testes.

The protective effect of thymoquinone was investigated against cadmium-induced testicular toxicity in rats. Testicular toxicity was induced by a single intraperitoneal (i.p.) injection of cadmium chloride (2mgkg(-1) ). Thymoquinone treatment (10mgkg(-1) day(-1) , i.p.) was applied for five consecutive days, starting 3days before cadmium administration. Thymoquinone significantly attenuated the cadmium-induced decreases in serum testosterone, and testicular reduced glutathione and superoxide dismutase activity and significantly decreased the elevations of testicular malondialdehyde, nitric oxide and cadmium ion levels resulted from cadmium chloride administration. Also, thymoquinone ameliorated the cadmium-induced testicular tissue injury observed by histopathological examination. In addition, thymoquinone significantly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumour necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in testicular tissue. It was concluded that thymoquinone, through its antioxidant and anti-inflammatory activities, may represent a potential candidate to protect the testes against the detrimental effect of cadmium exposure.

Simvastatin Treatment Ameliorates Injury of Rat Testes Induced by Cadmium Toxicity

Cadmium-induced testicular toxicity is mediated through oxidative stress and inflammation which eventually lead to cell death. Simvastatin, the antihyperlipidemic agent, exhibits additional antioxidant and anti-inflammatory activities. The aim of the present work was to investigate the protective effect of simvastatin against cadmium-induced testicular toxicity in rats. The rats received a single intraperitoneal (i.p.) injection of cadmium chloride (2mg/kg). Simvastatin treatment (5mg/kg/day, i.p.) was applied for three consecutive days, starting 1day before cadmium administration. Cadmium significantly decreased serum testosterone, and testicular reduced glutathione and catalase activity, and significantly increased testicular malondialdehyde, nitric oxide, and cadmium ion levels. Simvastatin significantly ameliorated the biochemical changes induced by cadmium. Cadmium-induced testicular tissue injury observed by histopathological examination was attenuated by simvastatin. In addition, simvastatin significantly decreased the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, nuclear factor-κB, and caspase-3, and increased heme oxygenase-1 expression in testicular tissue of rats exposed to cadmium toxicity. It was concluded that simvastatin, through its antioxidant and anti-inflammatory activities, provided a significant protective effect against cadmium-induced testicular toxicity in rats. However, starting treatment with simvastatin before cadmium exposure, as done in the present work, is not clinically applicable. Therefore, other investigations are needed to assess the protective effect of simvastatin treatment following induction of cadmium testicular toxicity.

DNA damage in thymocytes of mice after exposure of the whole body to combined action of cadmium ions and γ radiation

The effect of combined action of cadmium chloride at a dose of 0.5 mg/kg of body weight and γ-radiation of 1 Gy on induction of DNA damage in thymocytes and the total number of cells in the thymus of mice was studied. We found that injection of CdCl2 0.5 h prior to irradiation decreased the number of single-strand DNA breaks and the number of alkali-labile sites in thymocytes 48 h after irradiation as compared to the γ-radiation effect only. This effect was associated with a strong decrease in the total number of thymocytes in this organ as compared to the action of cadmium ions and γ radiation separately. This masked the general genotoxic effect of combined treatment and created an illusion of a radioprotective effect of cadmium ions. Injection of cadmium chloride into mice 24 h prior to irradiation was followed by an additive increase in the number of the single-strand DNA breaks and the number of alkali-labile sites in thymocytes as compared to the respective controls such as the separate effects of cadmium ions and irradiation. We revealed a simultaneous decrease in the part of DNA tightly bound to proteins, i.e., DNA-protein cross-links as compared to the effect of γ-radiation only. We did not observe any statistically significant changes in the total number of thymocytes as compared to the separate effects of cadmium ions and irradiation. Thus, our data show that exposure of murine thymocytes to combined action of cadmium ions and γ-radiation at the doses and with the methods of treatment used induced additive effects but not antagonistic effects or protection against radiation.

Captopril and telmisartan treatments attenuate cadmium‐induced testicular toxicity in rats

The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

Protective Effect of Zinc (Zn) on the Histology and Histochemistry of Liver and Kidney of Albino Rat Treated with Cadmium

The protective effect of zinc (Zn) on the liver and kidney of albino rats exposed to intraperitoneal injection of cadmium chloride (CdCl2) was studied. Light microscopic examination for rats which were injected intraperitonealy with of 0.16 mg CdCl2/kg of body weight for 8 weeks indicated severe histological changes in both liver and kidney. In liver, a blurred trabecular structure, vacuolar degeneration and increased density of nuclear chromatin with very compact nuclear structure were found in hepatocytes. Moreover; mononuclear cell infiltrations and necrosis of single cells were also observed. In the kidney tubules, degeneration and hypertrophy of epithelial cells and dilation in the glomeruli were also observed. The effects of cadmium on the ultrastructures of both organs were studied. There are ultrastructural damages appeared in both organs as nuclear membrane damage, chromatin condensation, swelling of the mitochondria with regression of mitochondrial cristae, degranulation and disintegration of protein-synthesizing structures such as rough endoplasmic reticulum, increased number of lysosomes and ultimately cell death. Zn partially alleviated the damage observed in both the liver and kidney and differences in histological structure has been observed between the Zn-Cd and the control groups. Our results demonstrate the protective effect of ZnCl2 in prevention CdCl2- induced significant toxic pathological changes in the liver and kidney of the albino rats.

Protective role of carnosine in mice with cadmium-induced acute hepatotoxicity

The hepatoprotective effect of carnosine was investigated against cadmium-induced acute liver injury in mice. Hepatotoxicity was induced by a single i.p. injection of cadmium chloride (6.5 mg/kg). Carnosine treatment (10 mg/kg/day, i.p.) was applied for three consecutive days, starting one day before cadmium administration. Carnosine significantly decreased the cadmium-induced elevations in serum aminotransferases. Carnosine suppressed lipid peroxidation and restored the deficits in the antioxidant defense mechanisms (reduced glutathione level, and catalase and superoxide dismutase activities) in liver tissue resulted from cadmium administration. Also, the reductions in hepatic nitric oxide and zinc ion levels, and the increases in hepatic cadmium ion concentration, and myeloperoxidase and caspase-3 activities following cadmium exposure were significantly attenuated by carnosine treatment. In addition, carnosine markedly ameliorated cadmium-induced liver tissue damage as evidenced by light and electron microscopic examinations. It was concluded that carnosine can be considered a potential candidate to protect the liver against the deleterious effect of acute cadmium intoxication.

Effect of cadmium on 17 beta-hydroxysteroid dehydrogenase in toad testis.

The enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) has been shown to exist biochemically and histochemically in the toad testis. A single injection of cadmium chloride (0.5 mg/toad) resulted 7 days later in reduced 17 beta-HSD activity in the testis and decreased serum testosterone with an increase in thumb pad glycogen content. It is concluded that cadmium induced changes lead to inhibition of androgen synthesis in the toad testis.

Protective effect of hemin against cadmium-induced testicular damage in rats

The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2 mg/kg). Hemin was given for three consecutive days (40 μmol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium.