RESUMEN
Exposure to mercuric chloride (HgCl2), either accidental or occupational, induces substantial liver and kidney damage. Coenzyme Q10 (CoQ10) is a natural antioxidant that also has anti-inflammatory and anti-apoptotic activities. Herein, our study aimed to investigate the possible protective effects of CoQ10 alone or loaded with albumin nanoparticles (CoQ10NPs) against HgCl2-induced hepatorenal toxicity in rats. Experimental animals received CoQ10 (10 mg/kg/oral) or CoQ10NPs (10 mg/kg/oral) and were injected intraperitoneally with HgCl2 (5 mg/kg; three times/week) for two weeks. The results indicated that CoQ10NP pretreatment caused a significant decrease in serum liver and kidney function markers. Moreover, lowered MDA and NO levels were associated with an increase in antioxidant enzyme activities (SOD, GPx, GR, and CAT), along with higher GSH contents, in both the liver and kidneys of intoxicated rats treated with CoQ10NPs. Moreover, HgCl2-intoxicated rats that received CoQ10NPs revealed a significant reduction in the hepatorenal levels of TNF-α, IL-1ß, NF-κB, and TGF-ß, as well as an increase in the hepatic level of the fibrotic marker (α-SMA). Notably, CoQ10NPs counteracted hepatorenal apoptosis by diminishing the levels of Bax and caspase-3 and boosting the level of Bcl-2. The hepatic and renal histopathological findings supported the abovementioned changes. In conclusion, these data suggest that CoQ10, alone or loaded with albumin nanoparticles, has great power in reversing the hepatic and renal tissue impairment induced by HgCl2 via the modulation of hepatorenal oxidative damage, inflammation, and apoptosis. Therefore, this study provides a valuable therapeutic agent (CoQ10NPs) for preventing and treating several HgCl2-induced hepatorenal disorders.
RESUMEN
Ferritinophagy is one of the most recent molecular mechanisms affecting cardiac function. In addition, it is one of the pathways by which doxorubicin, one of the anticancer drugs commonly used, negatively impacts the cardiac muscle, leading to cardiac function impairment. This side effect limits the use of doxorubicin. Iron chelators play an important role in hindering ferritinophagy. Antioxidants can also impact ferritinophagy by improving oxidative stress. In this study, it was assumed that the antioxidant function of melatonin could promote the action of deferoxamine, an iron chelator, at the level of ferritinophagy. A total of 42 male Wistar rats (150-200 g) were divided into seven groups (n = 6) which consisted of group I: control normal, group II: doxorubicin (Dox), group III: melatonin (Mel), group IV: deferoxamine (Des), group V: Mel + Dox, group VI: Des + Dox, and group VII: Mel + Des + Dox. Groups III, V and VII were orally pretreated with melatonin 20 mg/kg/day for 7 days. Groups IV, VI and VII were treated with deferoxamine at a 250 mg/kg/dose once on D4 before Dox was given. Doxorubicin was given at a 20 mg/kg ip single dose. On the 8th day, the rats were lightly anaesthetized for electrocardiography analysis and echocardiography. Serum samples were collected and then sacrificed for tissue sampling. The following biochemical assessments were carried out: PCR of NCOA4, IREB2, FTH1, SLC7A11, and GPX4; and ELISA for serum cTnI, serum transferrin, tissue GSH, and malondialdehyde. In addition, histopathological assessment of heart injury; immunostaining of caspase-3, Bax, and Bcl2; and physiological function assessment by ECG and ECHO were carried out. Doxorubicin-induced acute significant cardiac injury with increased ferritinophagy and apoptosis responded to single and combined prophylactic treatment, in which the combined treatment showed mostly the best results. In conclusion, using melatonin as an antioxidant with an iron chelator, deferoxamine, could hinder the hazardous cardiotoxic effect of doxorubicin. However, further studies are needed to detect the impact of higher doses of melatonin and deferoxamine with a prolonged treatment period.
RESUMEN
Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders. Coffee is a widely consumed beverage that enriched with antioxidants with numerous medicinal applications. Accordingly, the present study aimed to investigate the therapeutic potential of orally administered green coffee bean water extract (GCBWE) against cortical damage induced by high fat diet (HFD) followed by a single injection of streptozotocin (STZ) in rats. Metformin (Met) was used as standard antidiabetic drug. Animals were allocated into six groups: control, GCBWE (100 mg/kg), HFD/STZ (40 mg/kg), HFD/STZ + GCBWE (50 mg/kg), HFD/STZ + GCBWE (100 mg/kg) and HFD/STZ + Met (200 mg/kg) which were treated daily for 28 days. Compared to control rats, HFD/STZ-treated rats showed decreased levels of cortical dopamine, norepinephrine and serotonin with marked increases in their metabolites. Further, HFD/STZ treatment resulted in notable elevations in malondialdehyde, protein carbonyl and total nitrite levels paralleled with declines in antioxidant markers (SOD, CAT, GPx, GR and GSH) and down-regulations of Sod2, Cat, GPx1 and Gsr gene expression. Neuroinflammation was evident in diabetic animals by marked elevations in TNF-α, IL-1ß and up-regulation of inducible nitric oxide synthase. Significant rises incaspase-3 and Bax with decline in Bcl-2 level were noticed in diabetic rats together with similar results in their gene expressions. Cortical histopathological examination supported the biochemical and molecular findings. GCBWE administration achieved noteworthy neuroprotection in diabetic animals in most assessed parameters. The overall results suggested that antioxidant, anti-inflammatory; anti-apoptotic activities of GCBWE restored the cortical neurochemistry in diabetic rats.