CONSOLIDATED REPORT OF THE RESEARCH WORK DONE ON
                                                                          BIOCHEMICAL STUDIES
                                                                       ON THE CURATIVE EFFICACY OF
                                                                                 ASHSHIFA-500
                                                                (AN UNANI FORMULATION) SUPPLIED BY
                                                                AL-KAUSAR UNANI KIDNEY FOUNDATION
                                                                                    VANIYAMBADI

RESEARCH REPORT

Our day to day exposure to drugs and chemicals has put increasing demands on numerous organs of the body. Within these organs, the response of any given cell or tissue to an insult caused by a drug or chemical or it's metabolites is determined by the interplay of many factors. Because the urinary system is involved in eliminating toxic and waste substances, both drugs and chemicals may either generally or selectively damage the urinary system as filtration and excretion occur. Overt nephropathy, secondary to drug or chemical exposure occurs frequently and accounts for approximately 5% of all nephrology consultations and 20% to 30% of all cases of acute renal failure.

TREATMENT OF RENAL FAILURE

When the renal failure occurs, the more commonly adopted treatments in recent years are 1. Dialysis and in severe cases 2. Transplantation.

Since dialysis and transplantation have got their own limitations and drawbacks, search for new medicines, which cures kidney ailments, without any side effects still continues.

ASHSHIFA - 500 (UNANI FORMULATION)

Ashshifa-500 a coded drug by Alkausar Unani Kidney
Foundation, Vaniyambadi is a combination of herbs of 18 varieties and it is claimed to have an antinephrotoxic potency against acute and chronic renal failure.

GENTAMICIN - A POTENT NEPHROTOXIC AGENT

Gentamicin has been accepted as the antibiotic of choice in the treatment of serious pseudomonas and proteus infections. But this aminoglycoside shares the reputation of other aminoglycosides such as streptomycin and kanamycin for being potentially nephro & ototoxic. Rats treated with high dose gentamicin develope nonoliguric acute renal failure characterized by proximal tubular necrosis, depression of GFR and proimal tubular dysfunction.

ACUTE RENAL FAILURE
GENTAMICIN DOSAGE

In the present study, acute renal failure was induced transiently in rats by administering moderate and high dosages of gentamicin to decipher the antinephrotoxic potency of Ashshifa-500. Three different concentrations of gentamicin 40mg/kg bodywt twice daily for 15 days, 200mg/kg bodywt for 5 days, 400 mg/kg bodywt for 5 days were used to induce acute renal failure.

CHRONIC RENAL FAILURE
ADENINE DOSAGE

Animals with chronic renal failure were prepared by feeding them an 18% casein diet containing 0.75% adenine for 45 days. The animals were treated with Ashshifa-500 from 30th day till 45th day with a dose of 200mg/kg bodywt thrice daily.

TREATMENT WITH ASHSHIFA - 500

The effective dose of Ashshifa-500, to treatment renal disease has been derived as 200mg/kg body wt.

Non protein nitrogenous waste products such as urea, creatinine and uric acid which produce the clinical manifestation or uremia in renal failure was assessed in the blood and urine of azotemia animals before and after treatment with Ashshifa-500.

The elevated levels of uremic toxins were found to be reduced in both the acute and chronic renal failure after treatment with Ashshifa-500, due to the increased excretion of the same in the urine.

The effect of Ashshifa-500, on the accumulation of the lipid peroxide induced MDA content in the renal cortex and the activities of the free radical scavenging system such as SOD, CAT, GST and the content of the total GSH was studied in both acute & chronic renal failure groups.

Significant increase in the levels of lipid peroxides and decrease in the activities of the antioxidant enzymes observed during renal failure was found to be partly normalised after treatment with Ashshifa-500.

Histological studies were carried out on the renal cortex of acute chronic renal failure animals and compared with their corresponding Ashshifa-500 treated groups, to confirm the curative effect of Ashshifa-500 and its regenerative capacity towards the necrotic kidney tissues.

Increased percentage of renal tissue regeneration was evident from the renal histology observed after treatment with Ashshifa-500.

The activities of the pathophysiological enzymes such as LDH, SCOT, SGPT,. acid phosphatase and alkaline phosphatase, which would reflect the extent of tissue damage was assessed in both serum and in the renal cortex of experimental animals.

The regeneration was also evident from the results of the pathophysiological enzymes which showed increased activities in the renal tissues after treatment with Ashshifa-500.

The extent of regeneration produced after treatment with Ashshifa-500 was also assessed by measuring the activities of the ion transporting and membrane bound enzymes such as Na+ K+ ATPase, Ca2+ ATPase and Mg2+ ATPase in the tissue slices of the renal cortex.

The activities of ATPases in the kidney tissues were found to be increased after treatment with Ashshifa-500.

The activities of the citric acid cycle enzymes, which are used as a measure of mitochondrial membrance integrity, such as succinate Dehydrogenase, Malate Dehydrogenase, NADH Dehydrogenase, Cyt-C-oxidase, Isocitrate Dehydrogenase and - KG Dehydrogenase were also assayed In both acute and chronic renal failure groups.

The citric acid cycle enzyme were found to be increased compared to the toxic groups after treatment with Ashshifa-500.

Mitochondrial structural alterations observed during renal failure were minimized after the treatment period with Ashshifa-500.

Mitochondrial oxygen uptake and respiratory control ratio were examined by using biological oxygen electrode in the experimental groups of acute and chronic failure.

Ashshifa-500 produced an increased oxygen uptake and RCR when compared corresponding toxic groups.

Protein patterns for acute renal failure groups were obtained by poly Acrylamide Gel Electrophoresis (PAGE). Electrophoresis studies revealed similar jtion pattern in Ashshifa-500 and control groups.

Severity of anemia was compared among the renal failure groups. Anemia was found to be reduced after itment with Ashshifa-500.

The correlation between protenuric renal diseases and the hyperlipemia with corresponding alterations in the lipoprotein patterns have been studied in the chronic group. The Alternations were brought back to near normal condition
After treatment with Ashshifa-500.

The glycoprotein levels such as Hexose, hexosamine, fucose and sialic acid were estimated in the renal cortex of chronic experimental groups. The levels were found to be decreased during renal failure, but upon treatment with Ashshifa-500, the decreased levels were found to be normalised.