The effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso -2,3-dimercaptosuccinic acid (DMSA) on the nephrotoxicity in the mouse during repeated cisplatin (CDDP) treatments

Abstract

Previously, we reported that specific lower dose of sodium 2,3-dimercapto-1-propanesulfonic acid (DMPS) which is an antidote to heavy metal intoxication, inversely enhanced cisplatin (CDDP)-induced antitumor activity to S-180 cell-bearing mouse. This activity was only weak with meso-2,3-dimercaptosuccinic acid (DMSA), however. This study investigated the effects of lower doses of DMPS or DMSA on the nephrotoxicity and kinetics of CDDP. Kidney and blood isolated from female mice which received CDDP with or without DMPS or DMSA once daily for 4 days were provided for measuring levels of blood urea nitrogen (BUN) and transporter proteins (OCT2: organic cation transporter; MATE1: multidrug and toxin extrusion) mRNA, and CDDP-originated platinum, and TUNEL staining of renal tubular cells. DMPS or DMSA reduced effectively CDDP-induced BUN, and caused a moderate reduction of platinum in kidney. Additionally, both dimercapto-compounds restored the CDDP-reduced mRNA levels of transporter proteins (OCT2 and MATE1), and apparently suppressed the CDDP-induced apoptosis. These results suggest that DMPS, as well as DMSA, at approximate 17-fold dose (μmol/kg) of CDDP, has an enough potential to reverse the CDDP nephrotoxicity, and concomitant use of DMPS considering both dose and timing for administration is potentially useful for preventing nephrotoxicity and enhancing antitumor activity during CDDP chemotherapy.

Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins

“…Moreover, it has been studied as a candidate for acrolein detoxification as it can effectively reduce the acrolein concentration in vivo in murine because of its ability to bind to both the carbon double bond and aldehyde group of acrolein. The water-soluble, tissue-permeable and licensed metal chelator, 2,3-dimercaptopropane-1-sulfonic acid (DMPS), is also suitable for treating acute and chronic heavy metal intoxication including lead, mercury, cadmium and copper [48,49]. It was recently shown that both dimercaprol and DMPS displayed potential for repurposing as small molecule chelators to treat snake envenoming [20], most probably by chelating and removing Zn 2+ from the active site of Zn 2+ -dependent SVMPs.…”

Copper deposition in Wilson’s disease causes male fertility decline by impairing reproductive hormone release through inducing apoptosis and inhibiting ERK signal in hypothalamic-pituitary of mice

“…The current clinical treatment is mainly used to remove toxic copper stored in tissues, and copper complexing agents that promote copper excretion are mostly used 13,14). Sodium dimercaptopropane sulfonate is an oral metal chelating agent that can be excreted in complexes with a variety of heavy metals and is commonly used in the treatment of heavy metal poisoning, including those caused by lead, mercury, cadmium, and copper (15,16). Studies have shown that treatment with sodium dimercaptopropane sulfonate for copper drainage can reduce metal deposition in the brain, thus improving the corresponding neurological symptoms (17).…”