Nobiletin attenuates acetaminophen‐induced hepatorenal toxicity in rats

Abstract

The study aimed to examine the effects of nobiletin on the toxicity model induced with acetaminophen (APAP). For this purpose, 24 adult male rats were equally divided into four groups. The groups were the control group (group 1); dimethyl sulfoxide only, the APAP group (group 2) received a single dose of APAP 1000 mg/kg on the 10th day of experiment; the Nobiletin group (group 3), nobiletin (10 mg/kg) for 10 days; and the APAP + Nobiletin group (group 4), nobiletin (10 mg/kg) for 10 days with a single dose of APAP (1000 mg/kg) administered on the 10th day and the experiment ended after 48 hours. At the end of the study, a significant increase in malondialdehyde, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels and a significant decrease in glutathione levels, glutathione peroxidase activities and nuclear factor erythroid-derived 2-like 2 (Nrf-2) and heme oxygenase-1 (HO-1) expressions were observed with APAP application in liver and kidney tissues. Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, and creatinine levels were also significantly increased in the APAP group. However, nobiletin treatment in group 4 reversed oxidative stress and inflammatory and histopathological signs caused by APAP. It is concluded that nobiletin may be a beneficial substance that confers hepatorenal protection to APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms. K E Y W O R D Sacetaminophen, nobiletin, Nrf-2/HO-1, oxidative stress

Molecular, biochemical, and histopathological effects of long-term low and high-percentage fructose consumption on the liver in rats

“…Histopathological findings were evaluated according to the following criteria: Grade 0: Histopathological changes below 5%; Grade 1: Slight histopathological changes in between 5% and 33% of the total area; Grade 2: Moderate histopathological changes 7 in 33% to 66% of the total area; Grade 3: Severe histopathological changes in more than 66% of the total area (12).…”

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

“…We earlier mentioned that NOB is advantageous in suppressing iron overload-mediated oxidative stress. It is said that the high antioxidant activity of NOB results from improving the antioxidant defense system by targeting nuclear factor erythroid 2-related factor 2 (Nrf2) [75]. The activation of Nrf2 reduces ROS generation and oxidative stress via stimulation of superoxide dismutase, heme oxygenase-1, and NADPH quinone oxidoreductase 1 [75].…”

“…It is said that the high antioxidant activity of NOB results from improving the antioxidant defense system by targeting nuclear factor erythroid 2-related factor 2 (Nrf2) [75]. The activation of Nrf2 reduces ROS generation and oxidative stress via stimulation of superoxide dismutase, heme oxygenase-1, and NADPH quinone oxidoreductase 1 [75]. By induction of Nrf2, NOB decreases ROS levels to ameliorate hepatorenal toxicity [75].…”

“…The activation of Nrf2 reduces ROS generation and oxidative stress via stimulation of superoxide dismutase, heme oxygenase-1, and NADPH quinone oxidoreductase 1 [75]. By induction of Nrf2, NOB decreases ROS levels to ameliorate hepatorenal toxicity [75]. Another pathological condition that can be alleviated by NOB is ischemic/reperfusion (I/R) injury, a condition involved in enhancing oxidative stress and inflammation [76].…”

Neuroprotective effects of nobiletin on cerebral ischemia/reperfusion injury rats by inhibiting Rho/ROCK signaling pathway

“…The results of the present study showed that NOB reduced the levels of IL-6, IL-1β, and TNF-α in the serum of cerebral I/R injured rats, and the results of both histopathological and Nissl staining confirmed that NOB reduced neuron apoptosis in ischemic brain tissue. Likewise, several studies have indicated that NOB reduces the expressions of IL-6, IL-1β, and TNF-α in animal models of acute liver and kidney injury, aging, and osteoarthritis ( 35 - 37 ), and also decreases apoptosis in ischemic cardiomyocytes, hepatocytes, and neuron ( 14 , 38 , 39 ). All of this evidence demonstrates the great potential of NOB to be developed as a neuroprotective agent.…”