title: C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: A comparative efficacy evaluation with N-acetyl cysteine in adult rat brain.
abstract: Spirulina is a widely used health supplement and is a dietary source of C-Phycocyanin (CPC), a potent anti-oxidant. We have previously reported the neurotoxic potential of tributyltin chloride (TBTC), an environmental pollutant and potent biocide. In this study, we have evaluated the protective efficacy of CPC against TBTC induced neurotoxicity. To evaluate the extent of neuroprotection offered by CPC, its efficacy was compared with the degree of protection offered by N-acetylcysteine (NAC) (a well known neuroprotective drug, taken as a positive control). Male Wistar rats (28 day old) were administered with 20mg/kg TBTC (oral) and 50mg/kg CPC or 50mg/kg NAC (i.p.), alone or in combination, and various parameters were evaluated. These include blood-brain barrier (BBB) damage; redox parameters (ROS, GSH, redox pathway associated enzymes, oxidative stress markers); inflammatory, cellular, and stress markers; apoptotic proteins and in situ cell death assay (TUNEL). We observed increased CPC availability in cortical tissue following its administration. Although BBB associated proteins like claudin-5, p-glycoprotein and ZO-1 were restored, CPC/NAC failed to protect against TBTC induced overall BBB permeability (Evans blue extravasation). Both CPC and NAC remarkably reduced oxidative stress and inflammation. NAC effectively modulated redox pathway associated enzymes whereas CPC countered ROS levels efficiently. Interestingly, CPC and NAC were equivalently capable of reducing apoptotic markers, astroglial activation and cell death. This study illustrates the various pathways involved in CPC mediated neuroprotection against this environmental neurotoxicant and highlights its capability to modulate glial cell activity.
authors.affiliation: Immunotoxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India; Department of Biochemistry, Jamia Hamdard (Hamdard University), New Delhi, India; Department of Neurology, University of New Mexico, Building NRF, Room: 1131a, Albuquerque 87131, USA. Electronic address: msumonto@gmail.com.
authors.forename: Sumonto
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Department of Biochemistry, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Waseem A
authors.initials: WA
authors.lastname: Siddiqui
authors.affiliation: Immunotoxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India. Electronic address: shashik.iitr@gmail.com.
authors.forename: Shashi
authors.initials: S
authors.lastname: Khandelwal
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010798:Phycocyanin / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014220:Trialkyltin Compounds; D010798:Phycocyanin; C011559:tributyltin; D010088:Oxidoreductases; D005978:Glutathione; D000111:Acetylcysteine
keywords: Blood brain barrier; C-Phycocyanin; N-acetylcysteine; Neuroprotection; Oxidative stress; Tributyltin chloride