Arsenic reduces the antipyretic activity of paracetamol in rats: modulation of brain COX-2 activity and CB₁ receptor expression.
We examined whether subacute arsenic exposure can reduce paracetamol-mediated antipyretic activity by affecting COX pathway and cannabinoid CB1 receptor regulation. Rats were preexposed to elemental arsenic (4 ppm) as sodium arsenite through drinking water for 28 days. Next day pyrexia was induced with lipopolysaccharide and paracetamol's (200 mg/kg, oral) antipyretic activity was assessed. The activities of COX-1 and COX-2, the levels of PGE₂, TNF-α and IL-1β and expression of CB₁ receptors were assessed in brain. Arsenic inhibited paracetamol-mediated antipyretic activity. COX-1 activity was not affected by any treatments. Paracetamol decreased COX-2 activity, levels of PGE₂, TNF-α and IL-1β and caused up-regulation of CB1 receptors. Arsenic caused opposite effects on these parameters. In the arsenic-preexposed rats, paracetamol-mediated effects were attenuated, while CB₁ receptor up-regulation was reversed to down-regulation. Results suggest that elevated COX-2 activity and reduced CB₁ expression could be involved in the arsenic-mediated attenuation of the antipyretic activity of paracetamol.
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India.
Karunakaran
K
Vijayakaran
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India.
Kandasamy
K
Kannan
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India.
Manickam
M
Kesavan
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India.
Subramaniyam
S
Suresh
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India.
Palanisamy
P
Sankar
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India.
Surendra Kumar
SK
Tandan
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243122, Bareilly, Uttar Pradesh, India. Electronic address: snsarkar1911@rediffmail.com.
Souvendra Nath
SN
Sarkar
D000082:Acetaminophen / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D058633:Antipyretics / Q000494:pharmacology / Q000627:therapeutic use*; D001151:Arsenic / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004347:Drug Interactions; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
D058633:Antipyretics; D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D014409:Tumor Necrosis Factor-alpha; D014874:Water Pollutants, Chemical; D000082:Acetaminophen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D001151:Arsenic
Antipyretic activity; Arsenic; CB1 receptor; Cyclooxygenase; Paracetamol; Rat