P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats
To investigate combined effect of the anticancer drug cisplatin (CP) and the opiate analgesic morphine (MOR) on liver, rats were administered MOR (10 mg/kg/day i.p. for 10 days), with or without CP (7.5 mg/kg i.p. once at day 5 of the study). MOR or CP alone caused deterioration of liver function te...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Scientia Pharmaceutica |
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| Online Access: | https://www.mdpi.com/2218-0532/88/1/14 |
| _version_ | 1798000011612520448 |
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| author | Azza A.K. El-Sheikh |
| author_facet | Azza A.K. El-Sheikh |
| author_sort | Azza A.K. El-Sheikh |
| collection | DOAJ |
| description | To investigate combined effect of the anticancer drug cisplatin (CP) and the opiate analgesic morphine (MOR) on liver, rats were administered MOR (10 mg/kg/day i.p. for 10 days), with or without CP (7.5 mg/kg i.p. once at day 5 of the study). MOR or CP alone caused deterioration of liver function tests and induced damage to histological architecture of liver. In addition, each drug alone caused hepatic oxidative stress, as evident by significant increase of malondialdehyde and nitric oxide, as well as the significant decrease in GSH, catalase and SOD compared to control. Administration of either MOR or CP also caused liver inflammation, evident by the increase in the pro-inflammatory cytokines; TNF-α and IL-6. In addition, either MOR or CP induced liver apoptosis, as shown by significant increase in expression of the pro-apoptotic marker; caspase 3 compared to control. Either MOR or CP also caused up-regulation of the efflux transporter P-glycoprotein (P-gp). Combining MOR with CP caused deterioration in all parameters tested compared to CP alone. Thus, treatment with MOR worsened CP-induced hepatotoxicity through oxidative stress, inflammation and apoptosis mechanisms. In addition, both drugs contributed to the up-regulation of P-gp, which might be a new mechanism for their hepatotoxic effects. |
| first_indexed | 2024-04-11T11:13:29Z |
| format | Article |
| id | doaj.art-f591f69913124911a629f32221b9cdad |
| institution | Directory Open Access Journal |
| issn | 2218-0532 |
| language | English |
| last_indexed | 2024-04-11T11:13:29Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Scientia Pharmaceutica |
| spelling | doaj.art-f591f69913124911a629f32221b9cdad2022-12-22T04:27:19ZengMDPI AGScientia Pharmaceutica2218-05322020-03-018811410.3390/scipharm88010014scipharm88010014P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in RatsAzza A.K. El-Sheikh0Basic Health Sciences Department, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi ArabiaTo investigate combined effect of the anticancer drug cisplatin (CP) and the opiate analgesic morphine (MOR) on liver, rats were administered MOR (10 mg/kg/day i.p. for 10 days), with or without CP (7.5 mg/kg i.p. once at day 5 of the study). MOR or CP alone caused deterioration of liver function tests and induced damage to histological architecture of liver. In addition, each drug alone caused hepatic oxidative stress, as evident by significant increase of malondialdehyde and nitric oxide, as well as the significant decrease in GSH, catalase and SOD compared to control. Administration of either MOR or CP also caused liver inflammation, evident by the increase in the pro-inflammatory cytokines; TNF-α and IL-6. In addition, either MOR or CP induced liver apoptosis, as shown by significant increase in expression of the pro-apoptotic marker; caspase 3 compared to control. Either MOR or CP also caused up-regulation of the efflux transporter P-glycoprotein (P-gp). Combining MOR with CP caused deterioration in all parameters tested compared to CP alone. Thus, treatment with MOR worsened CP-induced hepatotoxicity through oxidative stress, inflammation and apoptosis mechanisms. In addition, both drugs contributed to the up-regulation of P-gp, which might be a new mechanism for their hepatotoxic effects.https://www.mdpi.com/2218-0532/88/1/14cisplatinhepatotoxicityil-6morphinep-glycoproteintnf-α |
| spellingShingle | Azza A.K. El-Sheikh P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats Scientia Pharmaceutica cisplatin hepatotoxicity il-6 morphine p-glycoprotein tnf-α |
| title | P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats |
| title_full | P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats |
| title_fullStr | P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats |
| title_full_unstemmed | P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats |
| title_short | P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats |
| title_sort | p glycoprotein abcb1 might contribute to morphine cisplatin induced hepatotoxicity in rats |
| topic | cisplatin hepatotoxicity il-6 morphine p-glycoprotein tnf-α |
| url | https://www.mdpi.com/2218-0532/88/1/14 |
| work_keys_str_mv | AT azzaakelsheikh pglycoproteinabcb1mightcontributetomorphinecisplatininducedhepatotoxicityinrats |