Cyto and Genoprotective Potential of Tannic Acid Against Cadmium and Nickel Co-exposure Induced Hepato-Renal Toxicity in BALB/c Mice.

Tannic acid (TA) is a metal chelating polyphenol that plays a crucial role in metal detoxification, but its modulatory role in co-exposure of these heavy metals' exposure needs to be explored. Cadmium (Cd) and nickel (Ni) are inorganic hazardous chemicals in the environment. Humans are prone to be exposed to the co-exposure of Cd and Ni, but the toxicological interactions of these metals are poorly defined. Present study was undertaken to study the preventive role of TA in Cd-Ni co-exposure-evoked hepato-renal toxicity in BALB/c mice. In the current investigation, increased oxidative stress in metal intoxicated groups was confirmed by elevated peroxidation of the lipids and significant lowering of endogenous antioxidant enzymes. Altered hepato-renal serum markers, DNA fragmentation, and histological alterations were also detected in the metal-treated groups. Present study revealed that Cd is a stronger toxicant than Ni and when co-exposure was administered, additive, sub-additive, and detrimental effects were observed. Prophylactic treatment with TA significantly reinstated the levels of lipid peroxidation (LPO), non-enzymatic, and enzymatic antioxidants. Moreover, it also restored the serum biomarker levels, DNA damage, and histoarchitecture of the given tissues. TA due to its metal chelating and anti-oxidative properties exhibited cyto- and genoprotective potential against Cd-Ni co-exposure-induced hepatic and renal injury.

Berberine affords protection against oxidative stress and apoptotic damage in F1 generation of wistar rats following lactational exposure to chlorpyrifos.

Chlorpyrifos (0,0-diethyl 0-(3,5,6-trichloro-2-pyridinyl)-phosphorothioate; (CPF)) is a widely used lipophilic organophosphorus insecticide that primarily manifests into central and peripheral nervous system toxicity. However, it is poorly investigated as a developmental neurotoxicant and thus remains less explored for pharmacological interventions as well. Berberine (BBR) is a benzylisoquinoline alkaloid, primarily found in the plants of Berberidaceae family, and is used for the synthesis of several bioactive derivatives. The goal of this study was to evaluate the CPF-induced neuronal damage through lactational route and analyze the neuroprotective efficacy of berberine (BBR), a potent antioxidant compound in the F1 generation. The environmentally relevant dose of CPF (3 mg/kg b.wt.) was administered via gavage to pregnant dams from postnatal day 1 to day 20 (PND 1-20). BBR (10 mg/kg b.wt.) was administered concurrently with CPF for the same duration as a co-treatment. Levels of reactive oxygen species, lipid peroxidation, membrane bound ATPases (Na+K+ATPase, Ca2+ATPase, and Mg2+ATPase), DNA damage, histomorphological alterations, cellular apoptosis were increased, and activities of glutathione reductase, endogenous antioxidant enzymes (SOD, CAT, GST, and GR) were decreased in cerebellum and cerebrum regions of CPF exposed pups. CPF triggered neuronal apoptosis by upregulating Bax and caspase-3 and downregulating Bcl-2. Co-treatment of BBR significantly attenuated these effects of CPF signifying oxidative stress mediated chlorpyrifos induced neuronal apoptosis. Berberine treatment ameliorated the CPF-induced downregulation of Bcl-2, Bax translocation, and up-regulation of caspase-3 in F1 pups. Therefore, BBR owing to its multiple pharmacological properties can be further explored for its therapeutic potential as an alternative neuroprotective agent against lactational exposure of chlorpyrifos-induced developmental neurotoxicity.

Epigallocatechin gallate attenuates arsenic induced genotoxicity via regulation of oxidative stress in balb/C mice.

Arsenic is well known genotoxicant which causes the excessive generation of reactive oxygen species (ROS) and inhibition of antioxidant enzyme systems leading to cell damage through the activation of oxidative sensitive signaling pathways. Epigallocatechin gallate (EGCG), the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, free radical scavenging and genoprotective activity in vivo. The present study attempted to investigate antioxidant and geno-protective efficacy of EGCG by regulating arsenic induced oxidative stress in mice. Animals received prophylactic and therapeutic treatments at two different doses (25 and 50 mg/kg b.wt.) of EGCG orally for 15 days and administered arsenic intraperitoneally at dose of 1.5 mg/kg b.wt (1/10th of LD50) for 10 days. Arsenic intoxication revealed enhanced ROS production (114%) in lymphocytes; elevated levels of LPO (2-4 fold); reduced levels of hepato-renal antioxidants (approx. 45%) and augmented genomic fragmentation in hepato-renal tissues; increased chromosomal anomalies (78%) and micronucleation (21.93%) in bone marrow cells and comet tailing (25%) in lymphocytes of mice. Both pre and post treatments of EGCG decreased ROS production, restored lipid peroxidation (LPO) and reduced hepato-renal antioxidants levels, reduced the DNA fragmentation, number of chromosomal aberrations (CA), micronucleation (MN), and comet tailing but prophylactic treatment of 50 mg/kg b.wt was the most effective treatment in regulating arsenic induced oxidative stress. The effectiveness of this dose was furthermore validated by calculating the inhibitory index. Thus, results of present work empirically demonstrate free radical scavenging, anti-oxidative and genoprotective efficacy of EGCG against arsenic toxicity.