Dose-Dependent Hydroquinone Liver Effects via SCD1/AMPK Pathway 🧬

 

INTRODUCTION 🧬

Hydroquinone (HQ), a widely used compound in industrial applications and dermatological treatments, poses potential risks to hepatic health that are not yet fully understood. Its metabolic fate and the mechanisms underlying its hepatotoxicity remain under investigation. This study aimed to elucidate the dose-dependent effects of HQ on liver function, particularly in relation to lipid metabolism and cellular stress responses. Using C57BL/6 mice, we administered HQ at concentrations of 0, 12.5, 25.0, and 50.0 mg/kg over a 13-week period. We performed comprehensive biochemical assays, RNA sequencing, and protein expression analysis to uncover the molecular mechanisms of HQ-induced liver injury. Notably, changes in lipid accumulation and liver enzyme activity were linked to distinct alterations in the SCD1/AMPK signaling axis. These findings contribute to a better understanding of HQ’s toxicological profile and highlight critical pathways that could serve as therapeutic targets or early biomarkers of hepatotoxicity.

DOSE-DEPENDENT EFFECTS OF HYDROQUINONE ON LIVER FUNCTION 🧪

The hepatotoxic impact of HQ varies significantly with dosage, as observed in this murine study. Low to moderate doses (12.5 and 25.0 mg/kg) primarily induced hepatic lipid accumulation, marked by elevated liver triglycerides (TG) and serum total cholesterol (TC), suggesting early-stage metabolic disturbance. Conversely, a high dose (50.0 mg/kg) triggered marked liver injury, as indicated by elevated serum liver enzymes, pointing to overt hepatocellular damage. These findings reveal that HQ's hepatotoxicity may progress from metabolic dysfunction to liver injury depending on the exposure level. This dose-responsive pattern reinforces the necessity of understanding both the threshold and cumulative effects of chemical agents like HQ in biological systems.

LIPID METABOLISM DISRUPTION INDUCED BY HYDROQUINONE 🧫

One of the primary manifestations of HQ exposure at lower concentrations was hepatic lipid accumulation. This was evidenced by increased levels of TG in the liver and TC in the serum, which suggest that HQ interferes with lipid homeostasis before inducing cell damage. The dysregulation of lipid metabolism could result from enhanced lipogenesis or impaired lipid degradation, with SCD1 playing a central role in this process. As lipid imbalance often precedes structural liver damage, these alterations may serve as early markers of HQ-induced toxicity. Further investigation into how HQ modifies fatty acid synthesis and storage is essential to decode the onset of liver dysfunction.

ROLE OF SCD1 IN HYDROQUINONE-INDUCED LIVER CHANGES 🧉

Stearoyl-CoA desaturase 1 (SCD1), a key enzyme in lipid metabolism, was found to be significantly upregulated at the mRNA and protein levels in response to 12.5 and 25.0 mg/kg HQ doses. This upregulation likely contributes to enhanced lipid synthesis and deposition within hepatocytes. SCD1's activity suggests a compensatory or pathological response to HQ-induced metabolic stress. As SCD1 overexpression is associated with lipogenesis, its role in HQ toxicity may involve creating an environment conducive to fat accumulation and subsequent liver stress. These findings highlight SCD1 as both a mediator and potential biomarker of early hepatotoxic effects caused by xenobiotic exposure.

ACTIVATION OF AMPK AND AUTOPHAGY UNDER HIGH-DOSE HQ STRESS ⚡

AMP-activated protein kinase (AMPK), an energy sensor in cells, showed increased activation in response to high-dose HQ exposure (50.0 mg/kg), suggesting an energy stress response. This was accompanied by enhanced autophagy, a cellular survival mechanism to mitigate damage under stress conditions. The induction of AMPK and autophagy implies a protective, adaptive cellular mechanism against acute chemical stress. It may serve to remove damaged organelles and maintain energy balance. Understanding how AMPK modulation influences hepatotoxicity offers promising avenues for therapeutic intervention, particularly in preventing irreversible liver injury following chemical exposure.

SCD1/AMPK SIGNALING AS A PROTECTIVE MECHANISM IN HQ TOXICITY 🧠

The interplay between SCD1 and AMPK in response to HQ exposure presents a complex but potentially protective signaling axis in the liver. While SCD1 is upregulated during early exposure, contributing to lipid dysregulation, AMPK activation in later stages acts as a compensatory mechanism to restore cellular energy balance and trigger autophagy. This dual-phase response suggests that the SCD1/AMPK pathway could serve as a biological switch in the transition from metabolic dysfunction to cellular injury. Targeting this pathway pharmacologically may open new doors to preventing or alleviating HQ-induced hepatotoxicity.

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#Hashtags

#Hydroquinone #LiverToxicity #Hepatotoxicity #SCD1 #AMPK #Autophagy #LipidMetabolism #ChemicalExposure #Toxicology #MurineModel #LiverInjury #FattyLiver #RNASeq #WesternBlot #DoseResponse #MetabolicStress #Biomarkers #CellSignaling #EnvironmentalToxicology #TherapeuticTargets