PABA Abstracts 1

© 2013

Mechanism of competitive inhibition of p-aminobenzoic acid oxidation by p-aminosalicylic acid

         (Durham and Hubbard 1960) Download

Effect of para-aminobenzoic acid on the course of retinal degeneration in the rd10 mouse

(Galbinur, Obolensky et al. 2009) Download

PURPOSE: Recent evidence suggests that oxidative injury plays a significant role in the pathogenesis of retinal degenerative diseases. Para-aminobenzoic acid (PABA) is a cyclic amino acid, which may act to decrease lipid peroxidation and oxidative injury. Our aim was to evaluate the efficacy of PABA in attenuating oxidative injury and rate of retinal degeneration in the rd10 mouse. METHODS: PABA (50 mg/kg) was administered intraperitoneally six times per week in 28 rd10 mice from postnatal day 3. Twenty-four littermate control mice were similarly injected with saline. At 3, 4.5, and 6 weeks of age, electrophysiological (full field electroretinogram-ERG), quantitative histological, and immunohistochemical techniques were used to assess the course and extent of retinal degeneration. Degree of lipid peroxidation was determined by the measurement of thiobarbituric acid reactive species (TBARS) and retinal carbonyl content was quantified using the 2,4-dinitrophenylhydrazine method. RESULTS: Dark adapted mixed rod-cone ERG responses at 3 weeks of age were higher in the PABA-treated group as compared to saline control (P < 0.05). By 4.5 weeks, this protective effect was largely abolished and by 6 weeks ERG was unrecordable in both groups. However, at both 3 and 4.5 weeks of age, light-adapted cone ERG amplitudes were better preserved in PABA-treated animals. At 4.5 weeks, thickness of the outer nuclear layer was 28.6% higher in the peripheral retina of PABA-treated mice as compared to controls (P < 0.05). Quantitative immunohistochemistry revealed 2.4-fold higher red/green cone opsin content in the retinas of PABA-treated mice (P < 0.005). At both 3 and 4.5 weeks, levels of TBARS and protein carbonyls were 49%-69% lower in PABA-treated retinas (P < 0.05-0.0005), suggesting less oxidative injury. CONCLUSIONS: PABA treatment may protect retinal function and attenuate the course of retinal degeneration in rd10 mice. Biochemical parameters indicate a lower degree of oxidative injury in PABA-treated retinas. PABA may potentially serve as an addition to antioxidative treatment for retinal and macular degenerations.


Improved specificity of the PABA test with p-aminosalicylic acid (PAS)

         (Hoek, van den Bergh et al. 1987) Download

Until now use of the PABA test together with [14C] PABA to calculate the PABA excretion index has probably been the best adaptation suggested to enhance the specificity of this non-invasive pancreatic function test. Drawbacks of the method are the application of radioactivity, the fact that children, pregnant women, and patients with renal insufficiency have to be excluded from the test, and the possible interference of drugs and isotopes. We propose simultaneous administration of p-aminosalicylic acid (PAS) in the PABA test and quantification of the urinary PABA and PAS excretion with liquid chromatography. Urinary PABA and PAS excretion in six hours are comparable (69.5 +/- 8.4% and 65.6 +/- 18.4% respectively in five healthy volunteers). Application of the PABA/PAS ratio was compared with the urinary PABA excretion in 21 normal controls, 38 patients with pancreatic disease, and 42 patients without pancreatic pathology. The PABA/PAS ratio and the per cent PABA excretion correlated very well in pancreatic patients: (PABA/PAS ratio) = 0.0149 (% PABA) + 0.052 (r = 0.902). Use of the PABA/PAS ratio enhanced the specificity of the test from 76 to 89%.

Simplified oral pancreatic function test.

         (Puntis, Berg et al. 1988) Download

The standard Bentiromide test and a new modified test using p-aminosalicylic acid (PAS) as a pharmacokinetic marker for p-aminobenzoic acid (PABA) have been evaluated in the detection of pancreatic exocrine insufficiency in children. The conventional two day test using a colorimetric assay for urinary PABA discriminated poorly between five children with pancreatic insufficiency and 13 others with normal pancreatic function. Two further groups of patients, comprising 28 with pancreatic exocrine insufficiency and 20 with normal pancreatic function underwent the modified test, and urine samples were analysed by high performance liquid chromatography. The results showed a complete separation between groups. The use of PAS eliminates a number of sources of error inherent in a two day Bentiromide test and provides a simplified and accurate diagnostic test for pancreatic insufficiency. The PABA-PAS modified test enables collection of the urine to be done during a single six hour period.


Acute hepatitis associated with treatment of Peyronie's disease with potassium para-aminobenzoate (Potaba)

         (Roy and Carrier 2008) Download

INTRODUCTION: Potassium para-aminobenzoate is an agent used in the treatment of sclerotic diseases including Peyronie's disease of the penis. It has been reported that this medication may have been responsible for cases of acute liver injury. AIM: To inform clinicians of the possibility of an adverse drug event associated with the oral intake of potassium para-aminobenzoate by reporting an additional case and compiling information from previous reports. METHODS: The affected patient's medical records were diligently reviewed; all available and relevant information pertaining to this adverse event is reported. Similar case reports were analyzed and compared, and relevant information was compiled in this report. RESULTS: The patient enjoyed a full biochemical recovery from his hepatitis 4 months after discontinuation of potassium para-aminobenzoate. CONCLUSION: To date, the oral use of potassium para-aminobenzoate has been reported to be linked to acute liver injury in six individuals. Appropriate management of this adverse drug event is the immediate discontinuation of the offending drug and general patient support measures.

The Biosynthesis Of P-Aminobenzoic Acid

            (Weiss and Srinivasan 1959) Download


The vitamin-like dietary supplement para-aminobenzoic acid enhances the antitumor activity of ionizing radiation

            (Xavier, Macdonald et al. 2006) Download

PURPOSE: To determine whether para-aminobenzoic acid (PABA) alters the sensitivity of tumor cells to ionizing radiation in vitro and in vivo. METHODS AND MATERIALS: Cellular proliferation was assessed by WST-1 assays. The effects of PABA and radiation on tumor growth were examined with chick embryo and murine models. Real-time reverse transcriptase-polymerase chain reaction and Western blotting were used to quantify p21CIP1 and CDC25A levels. RESULTS: Para-aminobenzoic acid enhanced (by 50%) the growth inhibitory activity of radiation on B16F10 cells, whereas it had no effect on melanocytes. Para-aminobenzoic acid enhanced (50-80%) the antitumor activity of radiation on B16F10 and 4T1 tumors in vivo. The combination of PABA and radiation therapy increased tumor apoptosis. Treatment of tumor cells with PABA increased expression of CDC25A and decreased levels of p21CIP1. CONCLUSIONS: Our findings suggest that PABA might represent a compound capable of enhancing the antitumor activity of ionizing radiation by a mechanism involving altered expression of proteins known to regulate cell cycle arrest.


The relation between sulfonamide resistance and p-aminobenzoic acid requirement

         (Yaniv and Davis 1953) Download

Antifibrotic Therapy with Potaba

         (Zarafonetis 1964) Download

Retrospective studies in scleroderma: effect of potassium para-aminobenzoate on survival

         (Zarafonetis, Dabich et al. 1988) Download

Demographic and survival data are presented for 390 patients with scleroderma. For the entire group an estimated 81.4% survived 5 years from diagnosis and 69.4% survived 10 years. Life-table analyses revealed that adequate treatment with potassium para-aminobenzoate (Potaba KPAB) was associated with improved survival (p less than 0.01); 88.5% 5 year survival rate and 76.6% 10 year survival rate for adequately treated patients. Five and ten year survival rates for patients never treated with KPAB were 69.8 and 56.6%, respectively. Similar findings were obtained by comparing observed to expected mortality for these patients; again, KPAB therapy showed prolongation of survival. The Cox proportional hazards model was also applied to this retrospective study adjusting for baseline clinical involvement, demographics and KPAB treatment. There were some interesting results including a high significance for skin involvement per se as a prognostic indicator: the greater the extent of skin involvement the poorer prognosis. Time from first diagnosis to first University Hospital visit or admission when included as a covariate did not influence survival.

Darkening of Gray Hair During Para-Amino-Benzoic Acid Therapy

            (Zarafonetis 1950) Download


References

Durham, N. N. and J. S. Hubbard (1960). "Mechanism of competitive inhibition of p-aminobenzoic acid oxidation by p-aminosalicylic acid." J Bacteriol 80: 225-31 PMID: 13725191

Galbinur, T., A. Obolensky, et al. (2009). "Effect of para-aminobenzoic acid on the course of retinal degeneration in the rd10 mouse." J Ocul Pharmacol Ther 25(6): 475-82 PMID: 20028256

Hoek, F. J., F. A. van den Bergh, et al. (1987). "Improved specificity of the PABA test with p-aminosalicylic acid (PAS)." Gut 28(4): 468-73 PMID: 3495472

Puntis, J. W., J. D. Berg, et al. (1988). "Simplified oral pancreatic function test." Arch Dis Child 63(7): 780-4 PMID: 3261963

Roy, J. and S. Carrier (2008). "Acute hepatitis associated with treatment of Peyronie's disease with potassium para-aminobenzoate (Potaba)." J Sex Med 5(12): 2967-9 PMID: 18624965

Weiss, B. and P. R. Srinivasan (1959). "THE BIOSYNTHESIS OF p-AMINOBENZOIC ACID." Proc Natl Acad Sci U S A 45(10): 1491-4 PMID: 16590531

Xavier, S., S. Macdonald, et al. (2006). "The vitamin-like dietary supplement para-aminobenzoic acid enhances the antitumor activity of ionizing radiation." Int J Radiat Oncol Biol Phys 65(2): 517-27 PMID: 16690434

Yaniv, H. and B. D. Davis (1953). "The relation between sulfonamide resistance and p-aminobenzoic acid requirement." J Bacteriol 66(2): 238 PMID: 13084564

Zarafonetis, C. J. (1950). "Darkening of gray hair during para-amino-benzoic acid therapy." J Invest Dermatol 15(6): 399-401 PMID: 14794992

Zarafonetis, C. J. (1964). "Antifibrotic Therapy with Potaba." Am J Med Sci 248: 550-61 PMID: 14224774

Zarafonetis, C. J., L. Dabich, et al. (1988). "Retrospective studies in scleroderma: effect of potassium para-aminobenzoate on survival." J Clin Epidemiol 41(2): 193-205 PMID: 3257255