Cadmium-induced Kidney Damage Research Articles

Masson pine pollen aqueous extract ameliorates cadmium-induced kidney damage in rats.

Introduction: Cadmium (Cd) is a hazardous environmental pollutant present in soil, water, and food. Accumulation of Cd in organisms can cause systematic injury and damage to the kidney. The Masson pine pollen aqueous extract (MPPAE) has attracted increasing attention due to its antioxidant activity and ability to enhance immunity. Methods: In this study, we investigated the potential of MPPAE to protect against Cd-induced kidney damage in rats and the underlying mechanism. The transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, were explored. Results: The concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were both significantly altered after treatment with MPPAE. Furthermore, sequencing and analysis of the transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, revealed differential expression of numerous genes and metabolites compared with the untreated control rats. These differentially expressed genes (DEGs) included detoxification-related genes such as cytochrome P450 and the transporter. The differentially expressed metabolites (DEMs) included 4-hydroxybenzoic acid, L-ascorbate, and ciliatine. Conjoint transcriptome and metabolome analysis showed that several DEGs were correlated with DEMs. Conclusion: These preliminary findings indicate the potential of MPPAE for the treatment of toxic metal poisoning.

The Protective Potential of Aronia melanocarpa L. Berry Extract against Cadmium-Induced Kidney Damage: A Study in an Animal Model of Human Environmental Exposure to This Toxic Element.

The impact of cadmium (Cd) on the function and structure of the kidney and the potential protective effect of an extract from Aronia melanocarpa L. berries were investigated in a rat model of low- and moderate-level environmental exposure to this heavy metal (1 and 5 mg Cd/kg feed for up to 24 months). The sensitive biomarkers of Cd-induced damage to the kidney tubules (N-acetyl-β-D-glucosaminidase (NAG), alkaline phosphatase (ALP), β2-microglobulin (β2-MG), and kidney injury molecule-1 (KIM-1) in the urine), clinically relevant early markers of glomerular damage (albumin in the urine and creatinine clearance), and other markers of the general functional status of this organ (urea, uric acid, and total protein in the serum and/or urine) and Cd concentration in the urine, were evaluated. The morphological structure of the kidney and inflammatory markers (chemerin, macrophage inflammatory protein 1 alpha (MIP1a), and Bcl2-associated X protein (Bax)) were also estimated. Low-level and moderate exposure to Cd led to damage to the function and structure of the kidney tubules and glomeruli. The co-administration of A. melanocarpa berry extract significantly protected against the injurious impact of this toxic element. In conclusion, even low-level, long-term exposure to Cd poses a risk of kidney damage, whereas an intake of Aronia berry products may effectively protect from this outcome.

Nutraceuticals as Alternative Approach against Cadmium-Induced Kidney Damage: A Narrative Review.

Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is the kidney, where it accumulates. In the present narrative review, we assessed experimental and clinical data dealing with the mechanisms of kidney morphological and functional damage caused by Cd and the state of the art about possible therapeutic managements. Intriguingly, skeleton fragility related to Cd exposure has been demonstrated to be induced both by a direct Cd toxic effect on bone mineralization and by renal failure. Our team and other research groups studied the possible pathophysiological molecular pathways induced by Cd, such as lipid peroxidation, inflammation, programmed cell death, and hormonal kidney discrepancy, that, through further molecular crosstalk, trigger serious glomerular and tubular injury, leading to chronic kidney disease (CKD). Moreover, CKD is associated with the presence of dysbiosis, and the results of recent studies have confirmed the altered composition and functions of the gut microbial communities in CKD. Therefore, as recent knowledge demonstrates a strong connection between diet, food components, and CKD management, and also taking into account that gut microbiota are very sensitive to these biological factors and environmental pollutants, nutraceuticals, mainly present in foods typical of the Mediterranean diet, can be considered a safe therapeutic strategy in Cd-induced kidney damage and, accordingly, could help in the prevention and treatment of CKD.

GC-MS analysis of aqueous extract of Nymphaea lotus and ameliorative potential of its biosynthesized gold nanoparticles against cadmium-induced kidney damage in rats

Plants possess compounds serving as reducing agents for green synthesis of gold nanoparticles (AuNPs), which is currently considered for biomedical application. Exposure to cadmium (Cd) can affect the functional integrity of the several organs such as kidney and liver. Nymphaea lotus (NL) is known for its several medicinal properties, including its protective role against tissue damages. This study investigated the bioactive compounds in NL using gas chromatography-mass spectroscopy (GC-MS) and ameliorative potential of its biosynthesized AuNPs (NL-AuNPs) against Cd-induced nephrotoxicity in rats. The presence of bioactive compounds in N. lotus was investigated by GC-MS in aqueous extract of NL. Gold nanoparticles were synthesized using aqueous extract of NL. Thirty rats were grouped into six (n = 5). Group 1 served as control, while group 2, 3, 4 and 5 received CdCl2 (10 mg/kg) orally for five days. Thereafter, groups 3, 4, and 5, respectively, received silymarin (75 mg/kg), 5 and 10 mg/kg NL-AuNPs, orally for 14 days, while group 6 received 10 mg/kg NL-AuNPs only. Rats were sacrificed after treatment, and biochemical parameters and kidney histopathology were evaluated. Bioactive compounds of pharmacological importance identified include pyrogallol, oxacyclohexadecan-2-one, 22-Desoxycarpesterol, 7,22-Ergostadienol, β-sitosterol and Dihydro-β-agarofuran. Cadmium caused nephrotoxicity in rats, as evidenced by significant (p < 0.05) increase in the levels of kidney function markers (serum urea and creatinine) and inflammatory markers (Interleukin-6 (IL-6) and Nuclear Factor-κB (NF-κB)) when compared with control. These changes were significantly (p < 0.05) ameliorated by the spherically-synthesized NL-AuNPs (25–30 nm) with the 5 mg/kg NL-AuNPs more potent against kidney damage induced by Cd in rats but high doses of NL-AuNPs (≥10 mg/kg) could be suggested toxic. NL possess phytochemicals capable of reducing gold salts to nanoparticle form, and doses up to 5 mg/kg could be considered safe for the treatment of renal damage occasioned by cadmium.

Synthesized gold nanoparticles mediated by Crassocephalum rubens extract down-regulate KIM-1/NGAL genes and inhibit oxidative stress in cadmium-induced kidney damage in rats

Cadmium (Cd) exposure induces kidney damage by mediating oxidative stress and inflammation. In this study, the role of Crassocephalum rubens-gold nanoparticles (C. rubens-AuNPs) in down-regulating kidney injury molecules-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) genes and inhibiting oxidative stress in Cd-induced kidney damage in rats was investigated. Thirty male Wistar rats were distributed randomly into six groups (n = 5). Group I served as control, while groups II, III, IV, and V rats were administered with 20 mg/kg b.w. cadmium chloride (CdCl2) for five consecutive days. Groups III, IV, and V rats were treated, 24 h after the last dose of CdCl2, with silymarin, 5 mg/kg and 10 mg/kg C. rubens-AuNPs, respectively, for 14 days. Group VI rats received 10 mg/kg C. rubens-AuNPs only for 14 days. Animals were sacrificed 24 h after the last dose of the treatment. Biochemical parameters such as kidney function markers, biomarkers of nephrotoxicity, and oxidative stress markers were assayed. Results indicated that 20 mg/kg b.w. CdCl2 caused kidney damage, as evidenced by significant (p < 0.05) increase in the levels of serum urea and creatinine, malondialdehyde, reduced level of superoxide dismutase (SOD), and increased mRNA expression of the kidney injury biomarkers (KIM-1 and NGAL genes), when compared with the control. However, these changes were attenuated by both doses of C. rubens-AuNPs when compared with Cd-induced nephrotoxic rats. It can be suggested that C. rubens-AuNPs have the potential to ameliorate kidney damage induced by Cd via oxidative stress inhibition and down-regulation of KIM-1/NGAL genes.

Role of Fucoxanthin towards Cadmium-induced renal impairment with the antioxidant and anti-lipid peroxide activities

ABSTRACT Kidney damages caused by cadmium are considered to be one of the most dangerous consequences for the human body. This study aimed to investigate the protective effects of fucoxanthin supplementation on mice models subjected to cadmium-induced kidney damage. The mice treated with cadmium chloride (CdCl2) were observed to have significantly reduced the cross-section area of glomeruli. Cadmium exposure has also caused the damage of the structural integrity of mitochondria and increased blood urea nitrogen (BUN), kidney injury molecule 1 (KIM1), and neutrophil gelatinase associated lipocalin (NGAL) levels. Peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) levels in cadmium-exposed mice were markedly declined. Caspase3, caspase8, and caspase9 gene expressions in association with apoptosis were dramatically elevated in renal tissues. The CdCl2 treated mice were orally administered with 50 mg/kg Shenfukang, 10 mg/kg, 25 mg/kg, and 50 mg/kg fucoxanthin for 14 days. The results revealed that high doses of fucoxanthin administration significantly decreased BUN, KIM1, NGAL levels, increasing POD, SOD, CAT, and ascorbate APX levels. Fucoxanthin administration also promoted recovery of the renal functions, micro-structural organization, and ultra-structural organization in the renal cells. In summary, the ameliorative effects of fucoxanthin supplementation against cadmium-induced kidney damage were mediated via inhibiting oxidative stress and apoptosis, promoting the recovery of structural integrity of mitochondria.

Aberrations in Renal Function Parameters Following Oral Administration of &amp;lt;i&amp;gt;Phyllanthus amarus&amp;lt;/i&amp;gt; in Cadmium-Induced Kidney Damage in Adult Wistar Rats

Renal disease has been found to be the ninth leading cause of death. Environmental pollution is a serious cause for concern nowadays and the exposure of humans to heavy metals released into the environment by several sources produces deleterious and lethal effects. Cadmium (Cd) which is a non-essential heavy metal known to possess toxic effects on living things can be found almost anywhere and its toxicity is of concern to industrial workers and all humans due to its use in some industrial products and also in agriculture. The chief organ of toxic impact in the human is the kidney, where the proximal tubule is a major target of Cd deposition. The present study investigated if ethanolic extract of Chanca Piedra (CP) (<i>Phyllantus amarus</i>) has any prophylactic or ameliorative effects against nephrotoxicity induced by cadmium sulphate in adult male Wistar rats. A total of forty-two (42) adult male Wistar rats were used for this study and were divided into seven (7) groups (n=6) as follows: Group A (control), Group B (40mg/kg BW), Group C (100mg/kg BW of CP and 40mg/kg BW of Cd), Group D (200mg/kg BW of CP and 40mg/kg BW), Group E (40mg/kg BW and 100mg/kg BW of CP), Group F (40mg/kg BW and 200mg/kg BW of CP), Group G (200mg/kg BW of CP). Both cadmium and Chanca Piedra were administered orally through oro-gastric cannula. Results showed that exposure to Cd lowered the activities of the kidney by increasing the plasma creatinine and urea levels. Exposure to CP also lowered the activities of the kidney by increasing the plasma creatinine and urea levels. The findings suggest that the administration of CP extract has no prophylactic or ameliorative effects on cadmium induced kidney damage and continue use of this extracts in the treatment of some diseases may be deleterious to the kidney.

Histomorphological Changes in Kidney Associated with the Ethanolic Extracts of the Leaves of &amp;lt;i&amp;gt;Phyllanthus amarus&amp;lt;/i&amp;gt; in Cadmium Induced Kidney Damage in Experimental Animals

Heavy metal poisoning is often as a result of prolonged occupational or domestic exposure to toxic metals and it is difficult to treat it immediately as the effects manifest over time. The use of herbal medicines and phytonutrients continues to expand rapidly across the world with many people now resorting to these products for treatment of various health challenges in different national healthcare settings. Chanca Piedra is a plant that has proven useful in assisting the treatment of various diseases. There have also been controversial claims on the effects of the plant on kidney stones and gall stones. Since cadmium is a very common nephrotoxic agent to which humans and animals are exposed frequently, this study has the potential to provide insight into the possible prophylactic and ameliorative effects of Chanca Piedra on kidney damage and it may also help in providing solutions to the problem of cadmium nephrotoxicity. The present study was carried out to investigate the prophylactic and ameliorative effects of orally administered ethanolic extract of Chanca Piedra (CP) (Phyllantus amarus) against nephrotoxicity produced by cadmium (40mg/kg BW) sulphate in adult male Wistar rats (Rattus novegicus). Forty-two (42) adult male Wistar rats were used in this study and were divided into seven (7) groups of (n=6) as follows: Group A (control), Group B (40mg/kg BW), Group C (100mg/kg BW of CP + 40mg/kg BW), Group D (200mg/kg BW of CP + 40mg/kg BW), Group E (40mg/kg BW + 100mg/kg BW of CP), Group F (40mg/kg BW + 200mg/kg BW of CP), Group G (200mg/kg BW of CP). Both cadmium and Chanca piedra were administered orally through oro-gastric cannula. The animals were sacrificed 24 hours after the last administration through cervical dislocation and blood samples were collected through cardiac puncture for analysis of superoxide dismutase and glutathione peroxidase and the kidney were fixed in 10% formal saline for 24hrs and then processed for histological analysis. Histological analysis using H&E stain for general histoarchitecture and Masson’s Trichrome for collagen fibres, indicated alterations in cell morphology of all the treated groups. The findings indicated that the administration of CP extract has no prophylactic or ameliorative effects on Cd-induced kidney damage and that CP had observable adverse effects on the kidneys of adult Wistar rats.

Protective effects of Chlorpromazine and Verapamil against cadmium-induced kidney damage in vivo

Overexposure to cadmium (Cd) can induce kidney damage, which was related to the oxidative damage and disturb intracellular Ca 2+ homeostasis. Chlorpromazine (CPZ), targeting calmodulin (CaM), and the Ca 2+ channel blocker Verapamil (Ver) are involved in intracellular Ca 2+ homeostasis processes. The aim of the study was to investigate the kidney damage caused by Cd administrated for 6 weeks and to evaluate the effects of pre-treatment with either chlorpromazine or verapamil on Cd-induced kidney damage. Thirty-two Wistar rats were divided randomly into 4 groups by weight, i.e., control group, Cd-treated group, and CPZ or Ver pre-treated group. The Cd-treated group rats were subcutaneously (s.c.) injected with 7 μmol CdCl 2/kg body weight/day. The CPZ and Ver pre-treated group rats were intraperitoneally (i.p.) injected with 5 mg CPZ/kg body weight/day, 4 mg Ver/kg body weight/day, respectively, 1 h before the s.c. administration of 7 μmol CdCl 2/kg body weight/day. The control group rats were injected s.c. with saline at the same time. The volume of injection was 2 ml/kg body weight, 5 times per week, for up to 6 weeks. After 6 weeks, Cd concentrations in the renal cortex and urine were significantly higher in Cd-treated group than that in controls. Cd concentrations of the urine in CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated group, but there were no significant changes in the renal cortex. Compared with the controls, urinary NAG, ALP activities, and the levels of GSH, MDA, and the activities of PKC, Na +–K +-ATPase, and Ca 2+-ATPase in rats from the Cd-treated group were significantly increased. SOD activity was suppressed by Cd. Urinary NAG activity and the level of GSH and the activities of PKC and Ca 2+-ATPase in both CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated rats. The present results showed that Cd-induced kidney damage was related to the oxidative damage and disturb intracellular Ca 2+ homeostasis. Both CPZ and Ver possess some ability to prevent cadmium-induced kidney damage via antioxidative action and by maintaining calcium homeostasis.

Plasma Metallothionein Antibody, Urinary Cadmium, and Renal Dysfunction in a Chinese Type 2 Diabetic Population

It has been reported that diabetes may increase the risk of cadmium-induced kidney damage. The presence of metallothionein antibody (MT-Ab) increased the susceptibility for tubular damage among cadmium workers. This study focused on the relationships between levels of MT-Ab, urinary cadmium, and kidney function in a Chinese type 2 diabetic population. A cross-sectional study was performed on 229 type 2 diabetic patients (92 men and 137 women) who were recruited from two community centers in one district of Shanghai City in China. Information was obtained from interviews, health records, and blood and urine samples. Levels of the tubular biomarker beta2-microglobulin increased significantly when the levels of MT-Ab and urinary cadmium were elevated in male and female subjects; in contrast, the levels of urinary albumin, a glomerular biomarker, did not display such a pattern. After adjusting for potential confounding covariates, logistic regression showed that the odds ratios (ORs) of tubular dysfunction increased upon 1) increasing the MT-Ab concentration from a low to high level (OR 5.56 [95% CI 2.25-13.73]) and 2) increasing the level of urinary cadmium from <1 to >or=1 microg/g creatinine (3.34 [1.17-9.53]); the OR of patients currently smoking was 3.51 (1.14-10.80) relative to that of those who had never smoked. This study proves that the presence of MT-Ab can potentiate tubular dysfunction among diabetic subjects and that patients with high MT-Ab levels are more prone to development of tubular damage.

Metals and Women's Health

There is a lack of information concerning whether environmental-related health effects are more or less prevalent or manifested differently in women compared to men. Previously, most research in the area of toxicology and environmental and occupational health involved male subjects. The present work aims at reviewing exposure and health effects of cadmium, nickel, lead, mercury, and arsenic manifested differently in women than in men. The gender difference in exposure to nickel results in a much higher prevalence of nickel allergy and hand eczema in women than in men. The internal cadmium dose is generally higher in women than in men, due to a higher gastro-intestinal absorption at low iron stores. This was probably one major reason why Itai-itai disease was mainly a woman's disease. Yet, data are sparse regarding the risk for women relative to men to develop cadmium-induced kidney damage in populations exposed to low levels of cadmium. Lead is accumulated mainly in bone and increased endogenous lead exposure has been demonstrated in women during periods of increased bone turnover, e.g., menopause. Both lead and mercury exposure in pregnant women has to be kept low in order to prevent neurodevelopment effects in the developing fetus and child. Limited data indicate that women are more affected than men following exposure to methylmercury at adult age, while males seem to be more sensitive to exposure during early development. Regarding arsenic, some data indicate gender differences in the biotransformation by methylation, possibly also in susceptibility to certain arsenic-related cancers. Obviously, gender-related differences in exposure and health effects caused by metals are highly neglected research areas, which need considerable focus in the future.

Follow up study of renal tubular dysfunction and mortality in residents of an area polluted with cadmium.

A retrospective cohort study was conducted to investigate the association between cadmium induced renal tubular dysfunction and mortality. A total of 230 subjects aged 40 or older and living in a cadmium polluted area in Kosaka Town, Akita Prefecture, Japan, were studied at least once between 1975 and 1977 and again in 1990. Urinary beta 2-microglobulin and total amino nitrogen concentrations were significantly related to mortality from all causes in women. The finding supports the idea that cadmium induced kidney damage is a factor associated with mortality in a general population exposed to environmental cadmium.

Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: decreased serum 1 alpha, 25-dihydroxyvitamin D level.

To investigate the mechanism for bone disease caused by exposure to cadmium serum samples were collected from 5 itai-itai disease patients, 36 Cd-exposed residents with renal tubular damage and 17 non-exposed individuals and analyzed for 1 alpha,25-dihydroxyvitamin D[1 alpha,25(OH)2D], parathyroid hormone, beta 2-microglobulin, calcium and inorganic phosphorus. Measurement of percentage tubular reabsorption of phosphate (%TRP) were performed only on the Cd-exposed subjects. Serum 1 alpha,25(OH)2D levels were lower in itai-itai disease patients and cadmium-exposed subjects with renal damage than in non-exposed subjects. Parathyroid hormone and beta 2-microglobulin concentrations in serum were higher in the Cd-exposed subjects. Decrease in serum 1 alpha,25(OH)2D levels were closely related to serum concentrations of parathyroid hormone, beta 2-microglobulin and %TRP. This study suggests that cadmium-induced bone effects were mainly due to a disturbance in vitamin D and parathyroid hormone metabolism, which was caused by the cadmium-induced kidney damage.