Tissue oxidative damage mediates impairment on phosphotransfer network during thymol intake: Effects on hepatic and...

Area of Science:

• Biochemistry
• Toxicology
• Cellular Biology

Background:

• Monoterpenes can cause organ damage by impairing mitochondrial energy production and adenosine triphosphate (ATP) synthesis.
• Bioenergetic homeostasis is crucial for cellular function and can be disrupted by toxins.
• The phosphotransfer network, involving enzymes like creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), plays a vital role in maintaining cellular energy balance.

Purpose of the Study:

• To investigate if the phosphotransfer network explains hepatic and renal bioenergetic impairment caused by thymol ingestion.
• To evaluate the impact of thymol on CK, AK, and PK activities in the liver and kidneys.
• To assess the role of oxidative stress and antioxidant capacity in thymol-induced renal damage.

Main Methods:

• Rats were administered daily oral doses of thymol (10, 20, or 40 mg/kg) for 30 days.
• Kidney and liver weights were measured.
• Activities of CK (cytosolic and mitochondrial) and PK were assayed in renal and hepatic tissues.
• Levels of reactive oxygen species (ROS), lipid damage, antioxidant capacity, and non-protein thiols were measured in renal tissues.

Main Results:

• A daily dose of 40 mg/kg thymol significantly reduced kidney weight.
• This high dose inhibited renal cytosolic and mitochondrial CK activity and renal PK activity.
• Thymol (40 mg/kg) increased renal ROS and lipid damage while decreasing antioxidant capacity and non-protein thiols.
• Lower doses (10 and 20 mg/kg) did not alter these parameters.
• No significant changes were observed in the liver.

Conclusions:

• High-dose thymol intake severely inhibits renal CK and PK activities, crucial for cellular energy homeostasis.
• Thymol disrupts communication between CK isoenzymes, impairing ATP regeneration and utilization.
• Renal CK and PK inhibition appears to be linked to increased oxidative stress and reduced antioxidant defenses in the kidney.