The potentially toxic effects of DMSO are the subject that virtually brought clinical investigations of DMSO to a standstill, but it is interesting to note that DMSO is of such low toxicity that grams per kilogram are used to measure toxicity instead of milligrams per kilogram as in the case of most other drugs. The toxic effects of DMSO vary with concentration, dosage, and route of administration.
Common complaints associated with the use of DMSO are the garlic-like breath odor, erythema, dryness, occasional pruritus associated with cutaneous administration, and diarrhea. In humans, headache,32 nausea, sedation, and less frequently, dizziness, are reported, and it is assumed that animals may experience similar phenomena. Urea-modified DMSO moderates some of these side effects. Urea-modified DMSO consists of 60- parts DMSO, 20-parts urea, and 20-parts water. This formula decreases the garlic or sulfur odor in the breath and the cutaneous irritation, pruritus, and dryness.
The oral LD50 of DMSO is higher than the intravenous LD50 and is approximately 10g/kg body weight.
The concentration of DMSO administered intravenously should not exceed 50%.
Since the potential for systemic toxicity is the greatest with intravenous administration of DMSO, the LD50 has been determined for several species and is in the range of 2.5- 8.9g/kg body weight. Symptoms at near lethal doses were similar in all species investigated and include spontaneous motor activity, tremors, muscular weakness,' prostration, transient convulsions, dyspnea, pulmonary edema, and hemorrhage.
With intravenous administration of DMSO it was found that there is no increased toxicity with repeated daily dosing, assuming that the repeated daily does not exceed the single maximum tolerated dose.
Damage to blood vessels due to DMSO is directly proportional to the concentration of DMSO and the number of repeated injections. The concentration of DMSO administered intravenously should not exceed 50% or the injected vessel may be subject to intimal damage, fibrosis, perivascular inflammation, and/or intravascular thrombi. However, no necrosis or sloughing of the blood vessel occurs. At or above the maximum tolerated dose there is a transient increase in respiratory rate, an increase in diuresis, and evidence of hemoglobinuria and bilirubinuria which are a direct result of erythrocyte damage and subsequent release of hemoglobin. Rapid intravenous administration of DMSO can induce seizures.
Local tissue reactions to subcutaneous or intramuscular injections are directly related to the concentration and total amount of DMSO injected. Reported responses to these injections include inflammatory, hemorrhagic, gelatinous, and edematous tissue reactions, but there is no abscess formation, necrosis, or sloughing. Intradermal injections of undiluted DMSO cause intense local vasoconstriction followed by hemorrhage and necrosis, and therefore, should be avoided.
Most biochemical changes associated with the administration of DMSO are related to the damage incurred by the red blood cells. This direct hemolytic effect is dose-related and is seen with intravenous DMSO in high concentrations or high dosage rates. Very high doses of oral DMSO cause hemorrhagic gastroenteropathy. Hemolysis results in reversible anemia with a reduction in hemoglobin in the circulating blood, hemoglobinuria, hematuria, and bilirubinuria. As a result of red blood cell damage, reticulocytosis and increased erythroid activity in the spleen and bone marrow are often observed.
MSO apparently has significant anti-inflammatory properties.
Researchers indicate that the anti-inflammatory effect of DMSO may be due to its ability to scavenge inflammation-triggering free radicals and/or its ability to inhibit the influx of polymorphonuclear cells and monocytes into the sites of inflammation.
One of the most popular uses of DMSO is for the treatment of acute swelling associated with traumatic injuries.
Another use of DMSO which utilizes its anti-inflammatory properties is in the treatment of toxic snake bites. It is thought that the use of DMSO decreases the swelling resulting from the snake bite, and it also potentiates the action of the administered corticosteroids. DMSO also decreases the inflammation associated with perivascular injections of thiacetarsamide sodium. DMSO decreases the swelling and dissipates this irritating antiparasitic, and thus prevents sloughing of surrounding tissues.
DMSO is also used in the treatment regime for otitis externa to reduce irritation. Treatment of ulcers and wounds is also augmented by DMSO therapy, in part due to its anti-inflammatory properties. The topical application of DMSO to canine mammary glands reduces swelling and engorgement.
DMSO has also been used to relieve post-operative pain and swelling following joint and tendon repair procedures.
DMSO injected subcutaneously in 10% concentration into cats produced a total loss of the central pain response. Two milliliters of 50% DMSO injected into the cerebrospinal fluid led to total anesthesia of the animal for 30 minutes. Complete recovery of the animal occurred without apparent ill effect.
DMSO remains the sole intravesical agent approved by the Food and Drug Administration (FDA) for the treatment of interstitial cystitis, and is often used in combination with other agents. It is also recommended by the European Association of Urology (EAU) for the treatment of BPS. However, these recommendations are based mostly on small randomized or non-placebo-controlled studies. The precise mechanism of action of DMSO is unknown; however, it is hypothesized to exert its clinical action by decreasing inflammation, triggering relaxation of bladder muscles, and influencing inflammatory mast cells.29 Typically, 50 mL of a 50% DMSO solution is instilled into the bladder via a temporary catheter. There is no standardized treatment regime, but it is typically administered once a week for 6 weeks. If a good response is achieved with this initial trial, a further 6-week course can be provided, followed by monthly maintenance.
Regardless of the route of administration of DMSO, a remarkable amount of radioactive DMSO is found in the plasma after only 30 minutes.
Cutaneous administration of DMSO generally results in lower serum levels than when DMSO is administered per os or intravenously. Maximal blood concentrations of DMSO applied cutaneously are reached in 2 hours.
An oral dose of 1g/kg-body weight results in peak plasma concentrations in 4 - 6 hours, and detectable levels persisted for 400 hours. The oral LD50 of DMSO is higher than the intravenous LD50 and is approximately 10g/kg body weight.
DMSO administered intravenously at the same dosage achieves higher plasma levels and is rapidly distributed throughout all tissues.
The concentration of DMSO administered intravenously should not exceed 50%.
Since the potential for systemic toxicity is the greatest with intravenous administration of DMSO, the LD50 has been determined for several species and is in the range of 2.5- 8.9g/kg body weight.
Local tissue reactions to subcutaneous or intramuscular injections are directly related to the concentration and total amount of DMSO injected. Reported responses to these injections include inflammatory, hemorrhagic, gelatinous, and edematous tissue reactions, but there is no abscess formation, necrosis, or sloughing. Intradermal injections of undiluted DMSO cause intense local vasoconstriction followed by hemorrhage and necrosis, and, therefore, should be avoided.
DMSO is often used as a delivery mechanism for water-insoluble drugs such as ISRIB.
With respect to the intact animal, the intravenous injection of 50 per cent DMSO in doses up to one g/kg did not alter the ECG of anesthetized dogs or monkeys. However, studies using the cat have shown that when sufficiently high doses were administered to this species, DMSO produced changes in the nervous, cardiovascular and respiratory systems.
At higher doses DMSO interfered with ganglionic and myoneural transmissions; apnea, hypotension and bradycardia were seen in cats following intravenous injection of 200 mg/kg, effects which were significantly attenuated by atropine. Fluid concentrations of 12% to 15% did not affect the capacity of perfused cardiac muscle to contract and concentrations up to 30% caused only minimal changes in capillary and mesentric circulation of a rodent species.
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