Due to its prevalence in aquatic environments and potential cytotoxicity, 4-nonylphenol (4-NP)
has garnered considerable attention. As a medicinal plant with numerous biological activities,
Nigella sativa (black seed or black cumin) seed (NSS) is widely utilized throughout the world.
Consequently, this study aimed to examine the potential protective effects of NSS against
4-NP-induced hepatotoxicity in African catfish (Clarias gariepinus). To achieve this objective, 18
fish (351 ± 3 g) were randomly divided into three equal groups for 21 days. The first group serves
as a control which did not receive any treatment except the basal diet. The second and third
groups were exposed to 4-NP at a dose of 0.1 mg L−1 of aquarium water and fed a basal diet only
or supplemented with 2.5% NSS, respectively. The histological, histochemical, and ultrastructural
features of the liver were subsequently evaluated as a damage biomarker of the hepatic tissue. Our
results confirmed that 4-NP was a potent hepatotoxic agent, as 4-NP-intoxicated fish exhibited
many lesions. Steatohepatitis, ballooning degeneration, sclerosing cholangitis, and coagulative
necrosis of melanomacrophagecenters (MMCs) were observed. Hemosiderin, lipofuscin pigments,
and proliferation of fibroblasts, kupffer cells, and telocytes were also demonstrated in the livers of
4-NP-intoxicated fish. In addition, decreased glycogen content and increased collagen deposition
were observed in the hepatic tissue. Hepatocytes exhibited ultrastructural alterations in the
chromatin, rough endoplasmic reticulum, smooth endoplasmic reticulum, mitochondria, lysosomes,
and peroxisomes. Co-administration of 2.5% NSS to 4-NP-intoxicated fish significantly reduced these
hepatotoxic effects. It nearly preserved the histological, histochemical, and ultrastructural integrity of
hepatic tissue.