The pyrethroid insecticide permethrin confers hepatotoxicity through DNA damage and mitochondria‐associated apoptosis induction in rat: Palliative benefits of Fumaria officinalis

Abstract

Permethrin (PER) is a pyrethroid pesticide that is extensively used as an insecticide in world because of its high activity and its low mammalian toxicity. The current study was conducted to investigate the protective action of Fumaria officinalis against PER‐induced liver injury in male rats. However, HPLC‐DAD showed the richness of 6 components in F. officinalis (F) including quercetin, ferulic acid, and naringenin which were the most abundant. Total polyphenols, total flavonoids, and condensed tannins were studied by phytochemical screening. In vitro, antioxidant properties showed that F. officinalis exhibited the highest DPPH radical, FRAP, and H2O2 tests and total antioxidant capacity. Wistar rats were divided into four groups: negative control group (C), positive control group (F) (200 mg F. officinalis/kg BW), PER group (34.05 mg permethrin/kg BW), and PER + F group (34.05 mg permethrin/kg BW and 200 mg F. officinalis/kg BW). Oral administration of PER led to promote a decrease of body weight and Ca2+‐ATPases and Mg2+‐ATPases activities and an increase of plasma C‐reactive protein level, transaminases, and hepatic ϒ‐GT activities as well as hepatic and mitochondrial oxidative stress. An increase in plasma lactate‐to pyruvate ratio and a reduction in complexes enzymes I, III, and IV activities were also observed. In addition, histoarchitecture of liver in PER‐treated rats showed apoptosis and necrosis as confirmed by DNA fragmentation. F. officinalis significantly exerted hepatoprotective effect by modulating hepatic alteration and mitochondrial dysfunction as well as genotoxicity. This effect could be attributed to phenolics compounds such as polyphenols, condensed tannins, and flavonoids.

Fumaria officinalis L. active compounds and biological activities: A review

“…The improvements were visible under liver histopathology analysis, which saw a significant recovery from the PER-induced vacuolation and fragmentation of chromatin. F. officinalis also significantly decreased the DNA damage induced by PER, which could be due to quercetin, which is known to protect liver cells against mercury-induced DNA injury and redox status alterations [14] . The ethanolic extract at a dose of 200 and 500 mg/Kg body weight, showed significant (p<0.001) action against carbon tetrachloride induced liver damage, by reducing the serum marker enzymes like SGPT, SGOT and ALP.…”

“…Scavenging activity of the extract on radicals with: IC 50 of 0.02 mg/g on DPPH, 0.01 mg/g on FRAP, and 0.14 mg/g on H2O2, which compares with IC 50 values of vitamin C of 0.014, 0.01 and 0.02 respectively. The total antioxidant capacity of F. officinalis extract was 258.79 mg GAE/g dry weight [14] .While some studies have found a correlation between the total amount of phenolics and the antioxidant activity, other studies have not found such correlation. This may be due to the presence of other antioxidant phytochemicals and synergistic effects among them, and to the fact that not all phenolic compounds have the same antioxidant activity.…”

“…The main individual active compounds in the plant were identified as quercetin-OHex-Hex (2.384 g/kg DM), quercetin O-Pen-Hex (3.5 g/kg DM), fumariline (1.728 g/kg DM) and caffeoylmalic acid (1.212 g/kg DM) [13] . In another study, the most abundant compounds overall were investigated using HPLC-DAD, showing the richness of 6 components in F. officinalis, in decreasing order: naringenin (5.78 mg/g extract), ferulic acid, quercetin, kaempferol, caffeic acid and rosmarinic acid (2.17 mg/g) [14] .…”

“…Three different studies by researchers in Tunisia have explored the protective effects of F. officinalis extract against mitochondrial bioenergetics disturbance and oxidative status perturbations induced by the insecticide permethrin (PER) both in the liver and in the kidneys. The protective effects could be attributed to phenolics compounds such as polyphenols, condensed tannins, and flavonoids, as well as to some of the plant's alkaloids [27,14,28] . In the study focusing on the liver, the extract significantly restored food intake, body weight and liver weight towards normal in the PER-treated rats.…”