Saffron and folic acid mitigate hepatic structural damage in IUGR rats via modulation of oxidative stress markers: A histological and molecular study
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Nur Aini Hasan
https://orcid.org/0009-0001-2582-4853
Viskasari Pintoko Kalanjati
https://orcid.org/0000-0002-7005-0025
Iswandi Erwin
https://orcid.org/0000-0001-6515-3380
Lucky Prasetiowati
https://orcid.org/0000-0002-8929-9816
Joni Susanto
https://orcid.org/0000-0001-8913-6622
Muhammad Miftahussurur
https://orcid.org/0000-0003-1415-6033
Abstract
One of the major causes of Intrauterine Growth Restriction (IUGR) in Indonesia is maternal malnutrition during pregnancy. Folic Acid has long been the primary supplement administered to women from preconception through pregnancy. Additionally, several studies have demonstrated that Saffron possesses anti-inflammatory and hepatoprotective properties. However, the effects of Saffron on liver tissue in IUGR rat models remain underexplored. This study aimed to investigate the effects of Saffron administration compared to Folic Acid on birth weight, hepatic tumor necrosis factor-alpha (TNF-α) expression, and liver histopathology in IUGR rats. Forty female and eight male rats were mated. Upon confirmation of pregnancy, the dams were randomly assigned to four groups: normal control (K1), receiving a standard diet throughout pregnancy (19-21 days) and lactation (21 days); IUGR control (K2), subjected to 50% dietary restriction (DR); IUGR + Saffron group (K3), receiving DR plus Saffron extract at 15.68 mg/kg body weight; and IUGR + Folic Acid group (K4), receiving DR plus Folic Acid at 1.5 mg/kg body weight. After 21 days of lactation, the offspring were euthanized, and liver tissues were collected for histological and immunohistochemical analyses. Pups' birth weights, hepatic TNF-α expression (immunohistochemistry), and histological damage (NAS score) were assessed. Folic acid showed superior effects in increasing birth weight, reducing TNF-α, and improving liver histology compared to saffron. These findings suggest folic acid as a potent hepatoprotective agent in IUGR conditions.
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Copyright (c) 2026 Nur Aini Hasan, Viskasari Pintoko Kalanjati, Iswandi Erwin, Lucky Prasetiowati, Joni Susanto, Muhammad Miftahussurur
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