Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice
Up to date, the management of hepatotoxicity induced by a suicidal or unintentional overdose of acetaminophen (APAP) remains a therapeutic challenge. The present study aimed to elucidate the potential effect of sitagliptin, a DPP-4 inhibitor, to ameliorate the acute injurious effects of acetaminophe...
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| Format: | Article |
| Language: | English |
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Universidade de São Paulo
2021-04-01
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| Series: | Brazilian Journal of Pharmaceutical Sciences |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502020000100610&tlng=en |
| _version_ | 1818367827532316672 |
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| author | Wafaa Ahmed Hewedy |
| author_facet | Wafaa Ahmed Hewedy |
| author_sort | Wafaa Ahmed Hewedy |
| collection | DOAJ |
| description | Up to date, the management of hepatotoxicity induced by a suicidal or unintentional overdose of acetaminophen (APAP) remains a therapeutic challenge. The present study aimed to elucidate the potential effect of sitagliptin, a DPP-4 inhibitor, to ameliorate the acute injurious effects of acetaminophen on the liver. APAP toxicity was induced in mice by an intraperitoneal injection of APAP (400 mg/kg). The effect of treatment with sitagliptin, initiated 5 days prior to APAP injection, was evaluated. Serum indices of hepatotoxicity, oxidative stress markers in liver tissues, serum IL-1β, and TNF-α in addition to hepatic- NF-E2-related factor-2 (Nrf2) were determined. Our results showed that APAP induced marked hepatic injury as evidenced by an increase in serum levels of ALT and AST, in addition to the deterioration of histological grading. Oxidative stress markers, serum TNF-α, and IL-1β were also elevated. Sitagliptin successfully ameliorated the histological changes induced by APAP, improving liver function tests and liver oxidant status accompanied with a marked increase in Nrf2 level in hepatic tissues. Thus, the hepatoprotective effects of sitagliptin in this animal model seem to involve Nrf2 modulation, coincidental with its anti-inflammatory and antioxidant effects. |
| first_indexed | 2024-12-13T22:58:14Z |
| format | Article |
| id | doaj.art-5f9de2cb1a24479587f66de5c0d6eccd |
| institution | Directory Open Access Journal |
| issn | 2175-9790 |
| language | English |
| last_indexed | 2024-12-13T22:58:14Z |
| publishDate | 2021-04-01 |
| publisher | Universidade de São Paulo |
| record_format | Article |
| series | Brazilian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-5f9de2cb1a24479587f66de5c0d6eccd2022-12-21T23:28:28ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902021-04-015610.1590/s2175-97902019000418482Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in miceWafaa Ahmed Hewedyhttps://orcid.org/0000-0002-8287-4179Up to date, the management of hepatotoxicity induced by a suicidal or unintentional overdose of acetaminophen (APAP) remains a therapeutic challenge. The present study aimed to elucidate the potential effect of sitagliptin, a DPP-4 inhibitor, to ameliorate the acute injurious effects of acetaminophen on the liver. APAP toxicity was induced in mice by an intraperitoneal injection of APAP (400 mg/kg). The effect of treatment with sitagliptin, initiated 5 days prior to APAP injection, was evaluated. Serum indices of hepatotoxicity, oxidative stress markers in liver tissues, serum IL-1β, and TNF-α in addition to hepatic- NF-E2-related factor-2 (Nrf2) were determined. Our results showed that APAP induced marked hepatic injury as evidenced by an increase in serum levels of ALT and AST, in addition to the deterioration of histological grading. Oxidative stress markers, serum TNF-α, and IL-1β were also elevated. Sitagliptin successfully ameliorated the histological changes induced by APAP, improving liver function tests and liver oxidant status accompanied with a marked increase in Nrf2 level in hepatic tissues. Thus, the hepatoprotective effects of sitagliptin in this animal model seem to involve Nrf2 modulation, coincidental with its anti-inflammatory and antioxidant effects.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502020000100610&tlng=enAcetaminophenDipeptidyl peptidase-4 inhibitorsHepatotoxicityNrf2Sitagliptin |
| spellingShingle | Wafaa Ahmed Hewedy Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice Brazilian Journal of Pharmaceutical Sciences Acetaminophen Dipeptidyl peptidase-4 inhibitors Hepatotoxicity Nrf2 Sitagliptin |
| title | Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice |
| title_full | Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice |
| title_fullStr | Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice |
| title_full_unstemmed | Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice |
| title_short | Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice |
| title_sort | effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice |
| topic | Acetaminophen Dipeptidyl peptidase-4 inhibitors Hepatotoxicity Nrf2 Sitagliptin |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502020000100610&tlng=en |
| work_keys_str_mv | AT wafaaahmedhewedy effectsoftreatmentwithsitagliptinonhepatotoxicityinducedbyacetaminopheninmice |