Sulforaphane ameliorate Arsenic induced cardiotoxicity in rats: Role of PI3k/Akt mediated Nrf2 signaling pathway.

Arsenic (As) toxicity can generate reactive free radicals, which play an important role in the evolution of cardiomyopathy. The aim of this research is to see if sulforaphane (SFN) protects against As-induced heart damage, oxidative stress, and mitochondrial complex dysfunction via the PI3K/Akt/Nrf2 signaling pathway. The rats were placed into four groups, each with eight rats. Group 1: Normal rats (control group); Group 2: Treatment group (5 mg/kg body weight); Group 3: SFN+As-treatment group (80 mg/kg body weight + 5 mg/kg body weight); Group 4: SFN group only (80 mg/kg body weight). The swot will last 4 weeks. At the end of the intermission (28 days), all of the rats starved overnight and killed with cervical decapitation. As administration considerably (p < 0.05) inflated the extent of free radicals (O2-, OH-), lipoid peroxidation (malondialdehyde, 4-hydroxynonenal), lipoid profile (low-density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol (VLDL-C), total cholesterol, triglyceride, and phospholipids), cardiac Troponin (cTnT&I), and Mitochondrial complex III. A noteworthy (p < 0.05) diminish the level of HDL-C, Mitochondrial complex I and II, enzymatic (superoxide dismutase, catalase, and glutathione peroxidase), and nonenzymatic antioxidant (glutathione and total sulfhydryl groups) and PI3k, Akt, and Nrf2 sequence in As treated rats. The western blot, real-time polymerase chain reaction, flowcytometric, and histology studies all corroborated the biochemical findings which revealed significant heart damage in rats. Pretreatment with SFN significantly (p < 0.05) reduced the invitro free radicals, lipid oxidative indicators, mitochondrial complex, lipid profiles, and increased phase II antioxidants in the heart. This result shows that dietary supplementation of SFN protects against As-induced cardiotoxicity via PI3k/Akt/Nrf2 pathway in rats.

Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish.

The safety of cyclophosphamide (CP) in the early developmental stages is not studied yet; it is important to study the responses at these stages because they might have relevance to CP-administered humans. We studied the developmental toxicity of CP by analysing physiological, morphological, and oxidative stress, neurotransmission enzymes, gene expression and histological endpoints in zebrafish embryos/larvae. The study lasted for 120 hpf at environmentally relevant concentrations of CP. No visible alterations were noticed in the control group. Delayed hatching, slow heart rate, yolk sac oedema, pericardial oedema, morphological deformities, the incompetence of oxidative stress biomarkers, excessive generation of ROS, apoptosis, inhibition of neurotransmitters and histopathological anomalies were observed in CP-treated groups. These alterations were found to be concentration- and duration-dependent effects for physiological and morphological endpoints, whereas concentration-dependent effects were antioxidants, ROS, apoptosis and histological endpoints. Biomarkers and gene expression were standardised using the integrated biomarker response-IBRv2 index. The IBRv2 index showed a concentration-dependent behaviour. A non-lethal developmental and teratogenic effect was observed in CP-treated zebrafish embryos/larvae at the studied concentrations. The studied biomarkers are sensitive, and the responses are interrelated; thus, their responses are useful to assess veiled and unseen hazards of pharmaceuticals.

Efficiency of hematological, enzymological and oxidative stress biomarkers of Cyprinus carpio to an emerging organic compound (alphamethrin) toxicity.

Alphamethrin is one of the extensively used pyrethroids. Its non-specific mode-of-action might affect the non-target-organisms. Its toxicity data on aquatic organisms are lacking. We determined the toxicity (35 days) of alphamethrin (0.6 µg/L and 1.2 µg/L) on non-target-organisms by evaluating the efficiency of hematological, enzymological and antioxidants biomarkers of Cyprinus carpio. Compared with the control group, the efficiency of the biomarkers studied was significantly (p < 0.05) impaired in the alphamethrin treated groups. Alphamethrin-toxicity altered hematology, transaminases and the potency of LDH of fish. ACP and ALP activity and biomarkers of oxidative stress in the gills, liver and muscle tissues were affected. IBRv2 index reveals that the biomarkers were inhibited. The observed impairments were the toxicity effects of alphamethrin with respect to concentration and time. The effectiveness of biomarkers for alphamethrin toxicity was like the toxicity data available on other banned insecticides. Alphamethrin could cause multiorgan toxicity on aquatic organisms at µg/L level.

A study to assess the health effects of an anticancer drug (cyclophosphamide) in zebrafish (Danio rerio): eco-toxicity of emerging contaminants.

Cyclophosphamide (CP) is widely used for treating various kinds of cancer. Because of its high intake, metabolism and excretion, these anticancer medications have been detected in the aquatic environment. There is very limited data on the toxicity and effects of CP on aquatic organisms. The present study aims to assess the toxic effect of CP on certain oxidative stress biomarkers (superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx, glutathione-GSH, glutathione S-transferases-GST and lipid peroxidation-LPO), protein, glucose, metabolising enzymes (aspartate aminotransferase-AST, alanine aminotransferase-ALT), and ion-regulatory markers (sodium ions-Na+, potassium ions-K+, and chloride ions-Cl-), and histology in the gills and liver of Danio rerio at environmentally relevant concentrations (10, 100 and 1000 ng L-1). Exposure to CP for 42 days led to a significant decrease in SOD, CAT, GST, GPx and GSH levels in the gills and liver tissues of zebrafish. The level of lipid peroxidation in the gills and liver tissues of zebrafish was significantly increased compared to the control group. Chronic exposure significantly changes protein, glucose, AST, ALT, Na+, K+ and Cl- biomarkers. Fish exposed to different levels of CP showed necrosis, inflammation, degeneration and hemorrhage in the gills and hepatic tissues. The observed changes in the studied tissue biomarkers were proportional to both dose and time. In conclusion, CP at environmentally relevant concentrations causes oxidative stress, energy demand, homeostasis disturbances, and enzyme and histological alterations in the vital tissues of zebrafish. These alterations were similar to the toxic effects reported in mammalian models.

Sulforaphane Potentially Ameliorates Arsenic Induced Hepatotoxicity in Albino Wistar Rats: Implication of PI3K/Akt/Nrf2 Signaling Pathway.

BACKGROUND/AIMS: Agriculture and industrial expansion in recent years have resulted in the undue discharge of arsenic into the environment, building arsenic toxicity a major worldwide anxiety. Oxidative stress is considered as the most conspicuous effect of arsenic toxicity. The current study was designed to evaluate the protective ability of sulforaphane (SFN) against arsenic (As) induced hepatotoxicity by activation of PI3K induced Akt and Nrf2 mediated signaling pathway. METHODS: For this purpose, male Wistar rats were randomly distributed into 6 groups of 8 rats each: control, Arsenic (5mg/kg BW), SFN plus Arsenic (20, 40, 80 mg/kg BW; 5mg/kg BW) and Vit. C plus Arsenic (100mg/kg BW; 5mg/kg BW). In this study, we have used spectrophotometry for enzymatic antioxidant assays, western blotting and PCR for protein and gene expression. Microtome for histological study. RESULTS: The arsenic-induced oxidative damage was confirmed by a significant (p<0.05) increase in the levels of ALAD, As concentration and depletion in the antioxidant content. Furthermore, Arsenics treatments significantly (p<0.05) increased the pro-apoptotic marker (Bax) and DNA damage, with decreased Nrf2 protein responsible for liver protection. However, pretreatment with SFN significantly (p<0.05) decreased the levels of ALAD, Arsenic concentration, and brought antioxidant enzymes into normal levels. This was accomplished by inhibition of apoptotic markers via activation of PI3K, Akt and Nrf2 mediated signaling pathway as evident from western blotting and PCR techniques. CONCLUSION: Moreover, SFN pretreatment shield the liver histoarchitecture observed in Arsenic treated groups suggesting prevention of liver toxicity via PI3K/Akt mediated Nrf2 signaling pathways and could possibly provide a protection against Arsenic induced hepatic burden.

Sulforaphane potentially attenuates arsenic-induced nephrotoxicity via the PI3K/Akt/Nrf2 pathway in albino Wistar rats.

Oxidative stress plays a significant role in the pathophysiology of numerous kidney diseases, generally mediated by reactive oxygen species (ROS). Arsenic (Ar) is known to exert its toxicity through the generation of ROS and inflammation. The current study investigates the protective effects of sulforaphane (SFN) against arsenic-induced renal damage via PI3K/Akt-mediated Nrf2 pathway signaling. Thirty-two male albino Wistar rats were randomly divided into four groups of eight animals each, designated as control, arsenic (Ar), sulforaphane plus Ar (SFN+Ar), and sulforaphane alone (SFN), with oral administration of Ar (5 mg/kg BW) and SFN (80 mg/kg BW) daily for 28 days. Ar administration significantly (P < 0.05) increased the levels of ROS, OHdG, Ar accumulation, and lipid peroxidation, and decreased levels of enzymatic and nonenzymatic antioxidants. Notably, a significant (P < 0.05) increase was observed in markers of apoptosis, DNA damage, TUNEL-positive cells, and dark staining of ICAM-1 in renal tissue with decreased PI3K/Akt/Nrf2 gene expression. The biochemical findings were supported by histopathological and electron microscopy evaluation, which showed severe renal damage in rats treated with Ar. Pretreatment with SFN significantly (P < 0.05) attenuated renal ROS, OHdG, lipid peroxidation, and DNA damage, and increased phase II antioxidants via PI3K/Akt-mediated Nrf2 activation in renal tissue. These results show that dietary supplementation with SFN protects against Ar-induced nephrotoxicity via the PI3K/Akt-mediated Nrf2 signaling pathway in the rat kidney.