The effects of quercetin on seizure, inflammation parameters and oxidative stress in acute on chronic tramadol intoxication.


Journal

BMC pharmacology & toxicology
ISSN: 2050-6511
Titre abrégé: BMC Pharmacol Toxicol
Pays: England
ID NLM: 101590449

Informations de publication

Date de publication:
19 10 2021
Historique:
received: 25 02 2021
accepted: 13 10 2021
entrez: 20 10 2021
pubmed: 21 10 2021
medline: 5 3 2022
Statut: epublish

Résumé

Tramadol is a widely used synthetic opioid for moderate to severe pain. Some studies have shown that tramadol can increase oxidative stress in different tissues of the body. Quercetin is also a substance with various biological effects, including antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, and cardioprotective activities. The current investigation aimed at determining the effects of quercetin, with or without naloxone, on tramadol intoxication. This study was performed on 30 male Wistar rats divided into five groups: Group I) control group: intraperitoneal injections of normal saline 0.9% for 14 days; Group II) tramadol: 25 mg/kg for 14 days, and then a 50 mg/kg acute dose injection on the last day; Group III) acute quercetin (single dose): tramadol injection as with the second group plus 100 mg/kg of quercetin on the last day; Group IV) chronic quercetin: tramadol injection similar to the second group plus quercetin 100 mg/kg for 14 days; Group V) quercetin plus naloxone: tramadol injection similar to the second group plus injection of quercetin 100 mg/kg + intravenous naloxone 2 mg/kg on the last day, followed by a 4 mg/kg/h injection of naloxone for six hours. The rats were monitored for six hours on the last day, relating to the number and severity of seizures. Finally, the samples were prepared for biochemical investigation of the serum level of oxidative stress markers (MDA, SOD, NOx), inflammatory factors (IL-6, TNF-α), biochemical parameters (ALT, AST, creatinine, glucose) and hematological assay. The liver, heart, kidney, cortex, cerebellum, and adrenal tissues were collected to investigate the redox state. None of the treatments had positive effects on the number and severity of seizures. Chronic administration of quercetin led to alteration of some blood parameters, including reduced hemoglobin level and elevated platelet counts. Acute on chronic tramadol administration resulted in a significant rise in AST, where different treatments failed to reduce their levels down to the control group. chronic administration of quercetin showed decreased oxidative/nitrosative stress in the liver, kidney, adrenal, and heart tissues. Quercetin plus naloxone decreased oxidative stress in the heart and adrenal tissues, but adverse effects on the brain cortex and hepatic function. Single-dose quercetin reduced cardiac oxidative stress.

Sections du résumé

BACKGROUND
Tramadol is a widely used synthetic opioid for moderate to severe pain. Some studies have shown that tramadol can increase oxidative stress in different tissues of the body. Quercetin is also a substance with various biological effects, including antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, and cardioprotective activities. The current investigation aimed at determining the effects of quercetin, with or without naloxone, on tramadol intoxication.
METHODS
This study was performed on 30 male Wistar rats divided into five groups: Group I) control group: intraperitoneal injections of normal saline 0.9% for 14 days; Group II) tramadol: 25 mg/kg for 14 days, and then a 50 mg/kg acute dose injection on the last day; Group III) acute quercetin (single dose): tramadol injection as with the second group plus 100 mg/kg of quercetin on the last day; Group IV) chronic quercetin: tramadol injection similar to the second group plus quercetin 100 mg/kg for 14 days; Group V) quercetin plus naloxone: tramadol injection similar to the second group plus injection of quercetin 100 mg/kg + intravenous naloxone 2 mg/kg on the last day, followed by a 4 mg/kg/h injection of naloxone for six hours. The rats were monitored for six hours on the last day, relating to the number and severity of seizures. Finally, the samples were prepared for biochemical investigation of the serum level of oxidative stress markers (MDA, SOD, NOx), inflammatory factors (IL-6, TNF-α), biochemical parameters (ALT, AST, creatinine, glucose) and hematological assay. The liver, heart, kidney, cortex, cerebellum, and adrenal tissues were collected to investigate the redox state.
RESULTS
None of the treatments had positive effects on the number and severity of seizures. Chronic administration of quercetin led to alteration of some blood parameters, including reduced hemoglobin level and elevated platelet counts. Acute on chronic tramadol administration resulted in a significant rise in AST, where different treatments failed to reduce their levels down to the control group.
CONCLUSION
chronic administration of quercetin showed decreased oxidative/nitrosative stress in the liver, kidney, adrenal, and heart tissues. Quercetin plus naloxone decreased oxidative stress in the heart and adrenal tissues, but adverse effects on the brain cortex and hepatic function. Single-dose quercetin reduced cardiac oxidative stress.

Identifiants

pubmed: 34666816
doi: 10.1186/s40360-021-00532-8
pii: 10.1186/s40360-021-00532-8
pmc: PMC8524995
doi:

Substances chimiques

Analgesics, Opioid 0
Thiobarbituric Acid Reactive Substances 0
Nitric Oxide 31C4KY9ESH
Tramadol 39J1LGJ30J
Malondialdehyde 4Y8F71G49Q
Quercetin 9IKM0I5T1E

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

59

Informations de copyright

© 2021. The Author(s).

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Auteurs

Samaneh Nakhaee (S)

Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS), Birjand, Iran.

Khadijeh Farrokhfall (K)

Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS), Birjand, Iran. kfarrokhfall@yahoo.com.

Ebrahim Miri-Moghaddam (E)

Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.

Mohsen Foadoddini (M)

Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.

Masoumeh Askari (M)

Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS), Birjand, Iran.

Omid Mehrpour (O)

Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS), Birjand, Iran. omid.mehrpour@yahoo.com.au.
Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA. omid.mehrpour@yahoo.com.au.

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Classifications MeSH