Interaction of plant lipids with 14 kDa phospholipase A2 enzymes

Several structurally related plant lipids were isolated and their effect was assessed on the enzyme activity of group I (pancreatic and Naja mocambique venom) and group II (Crotalus atrox venom) phospholipase A2 (PLA2) enzymes, with labelled Escherichia coli as an enzyme substrate. The neutral monogalactosyldiacylglycerol (MGDG) and negatively charged diacylglyceryl α-D-glucuronide (DGGA) did not influence the enzyme activity of either group. Digalactosyldiacylglycerol (DGDG), another uncharged glycolipid, inhibited PLA2 activity in a dose-dependent manner to 60–70% of the control. Sulphoquinovosyldiacylglycerol (SQDG), which is also anionic, activated both groups of PLA2 enzyme. A similar activation was observed with the zwitterionic diacylglyceryl-O-(N,N,N-trimethylhomoserine) (DGTS) and diacylglyceryl-O-(hydroxymethyl)(N,N,N-trimethyl)-β-alanine (DGTA). DGDG, SQDG and DGTS are dispersed homogeneously with low critical micelle concentrations (CMCs). The hydrodynamic radius of neutral DGDG is an order of magnitude larger than the charged lipids SQDG and DGTS. The inhibition of pig pancreatic PLA2 by DGDG was dependent on substrate concentration. The intrinsic fluorescence spectra of the enzyme was not changed in the presence of native or hydrogenated DGDG. Thus the inhibition is most probably due to a non-specific interaction of plant lipids with the substrate. Different lengths and saturations of the fatty acyl chains of DGDG did not alter the inhibition of PLA2, whereas deacylation abrogated the inhibitory effect. Both SQDG and DGTS activated pig pancreatic PLA2 in a dose-dependent manner. Saturation of the double bonds of these lipids decreased the activating effect. The fluorescence of pig pancreatic PLA2 incubated with SQDG and DGTS was enhanced by 2-fold and 3-fold respectively, suggesting the formation of a complex between enzyme and lipids. In conclusion, the effect of different plant lipids on PLA2 activity depends on different structural elements of the polar head group and their charge as well as the degree of unsaturation of the fatty acyl chains.

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Major proteins of bovine seminal plasma inhibit phospholipase A2

Biochemical Journal ◽

10.1042/bj3030121 ◽

1994 ◽

Vol 303 (1) ◽

pp. 121-128 ◽

Cited By ~ 25

Author(s):

P Manjunath ◽

S Soubeyrand ◽

L Chandonnet ◽

K D Roberts

Keyword(s):

Enzyme Activity ◽

Phospholipase A2 ◽

Seminal Plasma ◽

Inhibitory Activity ◽

Direct Interaction ◽

Inhibitory Effect ◽

Dependent Manner ◽

Pla2 Activity ◽

Sperm Capacitation ◽

Bsp Proteins

We have recently shown that the major proteins of bovine seminal plasma, namely BSP-A1, BSP-A2, BSP-A3 and BSP-30-kDa (collectively called BSP proteins) bind to spermatozoa and that the binding sites on the plasma membrane of spermatozoa are choline phospholipids. In view of the fact that these phospholipids are substrates for phospholipase A2 (PLA2), a key enzyme in sperm capacitation and the acrosome reaction, the effect of BSP proteins on this enzyme activity was investigated. Since these BSP proteins are ubiquitous, the effect on pig pancreatic PLA2 was also studied. In contrast with control proteins, when preincubated with phosphatidylcholine as substrate, all BSP proteins inhibited both pancreatic and sperm PLA2 activity in a dose-dependent manner and in the presence of 1-6 microM BSP protein the enzyme activity was completely abolished. When phosphatidylethanolamine was used as substrate, only pancreatic PLA2 was inhibited. On the other hand, when the BSP proteins were preincubated with the enzyme followed by addition of substrate, a biphasic effect was observed; there was stimulation of enzyme activity below 1.3 microM BSP followed by an inhibition above this concentration. The inhibitory activity was trypsin-sensitive but heat-resistant. The effect of co-incubation of heparin, which is implicated in sperm capacitation and which also interacts with BSP proteins, was studied. Heparin (10 microM) had no effect on the PLA2 inhibitory activity exhibited by all BSP proteins. The PLA2 inhibitory effect exhibited by BSP proteins was abolished with excess substrate. The BSP proteins were adsorbed on PLA2-agarose and could be affinity cross-linked to the enzyme, indicating a direct interaction of enzyme with the inhibitor. These results suggest that these BSP proteins modulate PLA2 activity and therefore, phospholipid metabolism.

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Effect of glucocorticoid on prostaglandin F2α-induced prostaglandin E2 synthesis in osteoblast-like cells: inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2

Acta Endocrinologica ◽

10.1530/eje.0.1310510 ◽

1994 ◽

Vol 131 (5) ◽

pp. 510-515 ◽

Cited By ~ 5

Author(s):

Osamu Kozawa ◽

Haruhiko Tokuda ◽

Atsushi Suzuki ◽

Jun Kotoyori ◽

Yoshiaki Ito ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Phospholipase A2 ◽

Phospholipase C ◽

Phospholipase A ◽

Phosphoinositide Hydrolysis ◽

Prostaglandin E ◽

Dependent Manner ◽

Kinase C ◽

Dose Dependent

Kozawa O, Tokuda H, Suzuki A, Kotoyori J, Ito Y, Oiso Y. Effect of glucocorticoid on prostaglandin F2α-induced prostaglandin E2 synthesis in osteoblast-like cells: inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2. Eur J Endocrinol 1994;131:510–15. ISSN 0804–4643 It is well known that osteoporosis is a common complication of patients with glucocorticoid excess. We showed previously that prostaglandin (PG) F2α stimulates the synthesis of PGE2, a potent bone resorbing agent, and that the activation of protein kinase C amplifies the PGF2α-induced PGE2 synthesis through the potentiation of phospholipase A2 activity in osteoblast-like MC3T3-E1 cells. In the present study, we examined the effect of dexamethasone on PGE2 synthesis induced by PGF2α in MC3T3-E1 cells. The pretreatment with dexamethasone significantly inhibited the PGE2 synthesis in a dose-dependent manner in the range between 0.1 and 10 nmol/l in these cells. This effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone also inhibited PGE2 synthesis induced by melittin, known as a phospholipase A2 activator. Furthermore, dexamethasone significantly inhibited the enhancement of PGF2α- or melittin-induced PGE2 synthesis by 12-O-tetradecanoylphorbol-13-acetate, known as a protein kinase C activator. In addition, dexamethasone significantly inhibited PGF2α-induced formation of inositol phosphates in a dose-dependent manner between 0.1 and 10 nmol/l in MC3T3-E1 cells. These results strongly suggest that glucocorticoid inhibits PGF2α-induced PGE2 synthesis through the inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2 in osteoblast-like cells. Osamu Kozawa, Department of Biochemistry, Institute for Developmental Research, Aichi Prefectural Colony, Kasugai, Aichi 480-03, Japan

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Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices

Biochemical Journal ◽

10.1042/bj2180069 ◽

1984 ◽

Vol 218 (1) ◽

pp. 69-74 ◽

Cited By ~ 12

Author(s):

Y Fujimoto ◽

N Akamatsu ◽

A Hattori ◽

T Fujita

Keyword(s):

Fatty Acids ◽

Prostaglandin E2 ◽

Phospholipase A2 ◽

Phospholipase C ◽

Unsaturated Fatty Acids ◽

Rabbit Kidney ◽

Dependent Manner ◽

Kidney Medulla ◽

Diacylglycerol Lipase ◽

Dose Dependent

We have investigated the effects of phospholipase A2 and C on the synthesis of prostaglandin E2 in rabbit kidney medulla and the release of fatty acids from the medulla slices. Exogenous phospholipase A2 [from Naja naja (Indian cobra) venom] and phospholipase C (from Clostridium welchii) stimulated prostaglandin E2 production in a dose-dependent manner. At the maximal effective concentrations (0.5 unit of phospholipase A2/ml, 2 units of phospholipase C/ml), phospholipase C increased prostaglandin E2 formation to the level observed with phospholipase A2. Phospholipase A2 enhanced the release only of unsaturated fatty acids, whereas phospholipase C stimulated the release of individual free fatty acids (C 16:0, C 18:0, C 18:1, C 18:2 and C 20:4). Moreover, p-bromophenacyl bromide inhibited phospholipase A2-stimulated prostaglandin E2 production and the release of fatty acids, but it had no influence on prostaglandin E2 formation and the release of fatty acids increased by phospholipase C, indicating that the stimulatory effect of phospholipase C is not mediated through the activation of endogenous phospholipase A2. These results suggest the presence of diacylglycerol lipase and monoacylglycerol lipase in the kidney and the importance of this pathway in prostaglandin synthesis by the kidney.

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Genetic or Enzymatic Disruption of Aromatase Inhibits the Growth of Ectopic Uterine Tissue

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.87.7.8683 ◽

2002 ◽

Vol 87 (7) ◽

pp. 3460-3466 ◽

Cited By ~ 34

Author(s):

Zongjuan Fang ◽

Sijun Yang ◽

Bilgin Gurates ◽

Mitsutoshi Tamura ◽

Evan Simpson ◽

...

Keyword(s):

Enzyme Activity ◽

Mouse Model ◽

Lesion Size ◽

Dependent Manner ◽

Wild Type ◽

Uterine Tissue ◽

Abdominal Organs ◽

Letrozole Treatment ◽

Key Enzyme ◽

Dose Dependent

Aromatase P450 (P450arom) is the key enzyme for the biosynthesis of estrogen that is essential for the growth of human endometriosis, a pathology characterized by endometrium-like tissue on the peritoneal surfaces of abdominal organs manifest by pelvic pain and infertility. Surgically transplanted autologous uterine tissue to ectopic sites on the peritoneum in mice has been used as an animal model to study endometriosis. Using this mouse model, we evaluated the roles of the P450arom gene and aromatase enzyme activity in the growth of endometriosis represented by ectopic uterine tissues in mice. Endometriosis was induced surgically in the following groups of mice: 1) untreated transgenic mice with disrupted P450arom gene (ArKO); 2) ArKO mice treated with systemic estrogen; 3) untreated wild-type (WT) mice; 4) WT mice treated with estrogen; 5) WT mice treated with the aromatase inhibitor, letrozole; and 6) WT mice treated with letrozole and estrogen. Each group contained eight mice; +/+ littermates of ArKO mice were used as WT controls. Treatment with estrogen increased the size of ectopic uterine tissues in ArKO and WT mice significantly. The ectopic uterine lesions in untreated and estrogen-treated ArKO mice were strikingly smaller than those in untreated and estrogen-treated WT controls, respectively. Systemic treatment of WT mice with letrozole significantly decreased the lesion size in a dose-dependent manner. The addition of estrogen to letrozole treatment increased the ectopic lesion size, although these lesions were significantly smaller than those in mice treated with estrogen only. As tissue controls, the effects of these conditions on normally located (eutopic) uterine tissue were evaluated. The effects of disruption of the P450arom gene and treatments with letrozole and estrogen seemed to be more profound on ectopic tissues, suggesting that ectopic tissues might be more sensitive to estrogen for growth. We conclude that both an intact P450arom gene and the presence of aromatase enzyme activity are essential for the growth of ectopic uterine tissue in a mouse model of endometriosis.

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Temperature-induced changes in lecithin model membranes detected by novel covalent spin-labelled phospholipids

Canadian Journal of Biochemistry ◽

10.1139/o77-027 ◽

1977 ◽

Vol 55 (2) ◽

pp. 173-185 ◽

Cited By ~ 14

Author(s):

L. Stuhne-Sekalec ◽

N. Z. Stanacev

Keyword(s):

Transition Temperature ◽

Fatty Acyl ◽

Model Membranes ◽

Head Group ◽

Polar Head Group ◽

Polar Group ◽

Conformational Isomers ◽

Hydrocarbon Chains ◽

Acyl Chains ◽

Induced Changes

Several spin-labelled phospholipids carrying covalently bound 5-doxylstearic acid (2-(3-carboxydecyl)-2-hexyl-4,4-dimethyl-3-oxazolidinoxyl) were intercalated in liposomes of saturated and unsaturated lecithins. Temperature-induced changes of these liposomes, detected by the spin-labelled phospholipids, were found to be in agreement with the previously described transitions of hydrocarbon chains of host lecithins detected by different probes and different techniques, establishing that spin-labelled phosopholipids are sensitive probes for the detection of temperature-induced changes in lecithin model membranes. In addition to the detection of already-known transitions in lecithin liposomes, the coexistence of two distinctly different environments was observed above the characteristic transition temperature. This phenomenon was tentatively attributed to the influence of the lecithin polar group on the fluidity of fatty acyl chains near the polar group. Combined with other results from the literature, the coexistence of two environments could be associated with the coexistence of two conformational isomers of lecithin, differing in the orientation of the polar head group with respect to the plane of bilayer. These findings have been discussed in view of the present state of knowledge regarding temperature-induced changes in model membranes.

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Lipid conformation in model membranes and biological membranes

Quarterly Reviews of Biophysics ◽

10.1017/s0033583500000305 ◽

1980 ◽

Vol 13 (1) ◽

pp. 19-61 ◽

Cited By ~ 589

Author(s):

Joachim Seelig ◽

Anna Seelig

Keyword(s):

Liquid Crystalline ◽

Double Helix ◽

Liquid Paraffin ◽

Biological Membranes ◽

Fatty Acyl ◽

Head Group ◽

Exact Nature ◽

Polar Head Group ◽

Acyl Chains ◽

Lipid Conformation

Protein molecules in solution or in protein crystals are characterized by rather well-defined structures in which α-helical regions, β-pleated sheets, etc., are the key features. Likewise, the double helix of nucleic acids has almost become the trademark of molecular biology as such. By contrast, the structural analysis of lipids has progressed at a relatively slow pace. The early X-ray diffraction studies by V. Luzzati and others firmly established the fact that the lipids in biological membranes are predominantly organized in bilayer structures (Luzzati, 1968). V. Luzzati was also the first to emphasize the liquid-like conformation of the hydrocarbon chains, similar to that of a liquid paraffin, yet with the average orientation of the chains perpendicular to the lipid–water interface. This liquid–crystalline bilayer is generally observed in lipid–water systems at sufficiently high temperature and water content, as well as in intact biological membranes under physiological conditions (Luzzati & Husson, 1962; Luzzati, 1968; Tardieu, Luzzati & Reman, 1973; Engelman, 1971; Shipley, 1973). In combination with thermodynamic and other spectroscopic observations these investigations culminated in the formulation of the fluid mosaic model of biological membranes (cf. Singer, 1971). However, within the limits of this model the exact nature of lipid conformation and dynamics was immaterial, the lipids were simply pictured as circles with two squiggly lines representing the polar head group and the fatty acyl chains, respectively. No attempt was made to incorporate the well-established chemical structure into this picture. Similarly, membrane proteins were visualized as smooth rotational ellipsoids disregarding the possibility that protruding amino acid side-chains and irregularities of the backbone folding may create a rather rugged protein surface.

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Biosynthesis of platelet-activating factor (PAF) in human polymorphonuclear leucocytes. The role of lyso-PAF disposal and free arachidonic acid

Biochemical Journal ◽

10.1042/bj2680091 ◽

1990 ◽

Vol 268 (1) ◽

pp. 91-98 ◽

Cited By ~ 18

Author(s):

M D C Garcia ◽

S Fernandez-Gallardo ◽

M A Gijon ◽

C Garcia ◽

M L Nieto ◽

...

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Phospholipase A2 ◽

Platelet Activating Factor ◽

Inhibitory Effect ◽

Eicosatetraenoic Acid ◽

Polymorphonuclear Leucocytes ◽

Maximal Effect ◽

Dependent Manner ◽

Dose Dependent

Theophylline and 1-methyl-3-isobutylxanthine (MIX), compounds that block eicosanoid formation and modulate phospholipase A2 activity, inhibited in a dose-dependent manner the formation of both leukotriene B4 (LTB4) and platelet-activating factor (PAF) by human polymorphonuclear leucocytes (PMN) in response to ionophore A23187. Theophylline and MIX lacked any inhibitory effect on acetyl-CoA: lyso-PAF acetyltransferase activity, which is the rate-limiting step for PAF biosynthesis in PMN. The effect of theophylline and MIX on PAF formation could be reversed by incubating the cells in the presence of 1-10 microM exogenous lyso-PAF. Incubation of PMN homogenates in the presence of unsaturated non-esterified fatty acids resulted in dose-dependent inhibition of the acetyltransferase. This effect was linked to the presence of a free carboxyl group, since both arachidonic acid methyl ester and palmitoyl-arachidonoyl phosphatidylcholine lacked inhibitory activity. This inhibitory effect was also dependent on the number of double bonds, since arachidonic acid (C20:4) and eicosapentaenoic acid (C20:5) displayed maximal effect. Kinetic analysis showed that the effect of arachidonic acid was consistent with competitive inhibition, with a Ki value of about 19 microM. Oxidative metabolites of arachidonic acid showed a lesser inhibitory effect with the following order of potency: arachidonic acid greater than 15-HETE (15-hydroxy-6,8,11,14-eicosatetraenoic acid) greater than LTB4 greater than 5-HETE (5-hydroxy-6,8,11,14-eicosatetraenoic acid) greater than lipoxin A4. Examination of enzymes involved in CoA-dependent acylation revealed a low activity of both arachidonoyl-CoA synthetase and arachidonoyl-CoA: lyso-PAF arachidonoyltransferase. These data indicate a strong influence on PAF biosynthesis of the products of the phospholipase A2 reaction, with lyso-PAF disposal being a critical event for PAF formation, and unsaturated fatty acids acting as feed-back inhibitors. The conversion of arachidonic acid via oxidative metabolism into less active inhibitors of acetyl-CoA:lyso-PAF acetyltransferase seems to be an additional mechanism of modulation of this enzyme activity, linked to the function of lipoxygenases. Finally, the enzyme activities involved in arachidonoyl-CoA-dependent acylation of lyso-PAF show a low efficiency in capturing arachidonic acid.

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Effect of diarachidonin on prostaglandin E2 synthesis in rabbit kidney medulla slices

Biochemical Journal ◽

10.1042/bj2320625 ◽

1985 ◽

Vol 232 (3) ◽

pp. 625-628 ◽

Cited By ~ 3

Author(s):

Y Fujimoto ◽

H Uno ◽

C Kagen ◽

T Ueno ◽

T Fujita

Keyword(s):

Arachidonic Acid ◽

Phosphatidic Acid ◽

Prostaglandin E2 ◽

Phospholipase A2 ◽

Rabbit Kidney ◽

Dependent Manner ◽

Kidney Medulla ◽

Sequential Action ◽

Acid Release ◽

Dose Dependent

The effect of diarachidonin on the synthesis of prostaglandin E2 in rabbit kidney medulla slices was examined. The addition of diarachidonin stimulated prostaglandin E2 production in a dose-dependent manner. At three concentrations (10, 50 and 100 microM), increases in prostaglandin E2 formation induced by exogenous diarachidonin were 2-fold greater than those induced by exogenous arachidonic acid. Diacylglycerol or phosphatidic acid from egg lecithin had little or no effect on prostaglandin E2 production. Moreover, EGTA failed to inhibit diarachidonin-stimulated prostaglandin E2 formation, indicating that the stimulatory effect of diarachidonin is not mediated through the activation of endogenous phospholipase A2 (including phosphatidic acid-specific phospholipase A2). These results are discussed in the light of our former hypothesis that arachidonic acid release from kidney medulla phospholipids might occur through the sequential action of a phospholipase C coupled to diacylglycerol and monoacylglycerol lipases [Fujimoto, Akamatsu, Hattori & Fujita (1984) Biochem. J. 218, 69-74].

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Influence of arachidonic acid on indices of phospholipase A2 activity in the human neutrophil

Biochemical Journal ◽

10.1042/bj2910825 ◽

1993 ◽

Vol 291 (3) ◽

pp. 825-831 ◽

Cited By ~ 23

Author(s):

J D Winkler ◽

C M Sung ◽

W C Hubbard ◽

F H Chilton

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Protein Kinase ◽

Phospholipase A2 ◽

Human Neutrophils ◽

Maximal Effect ◽

Dependent Manner ◽

Pla2 Activity ◽

Tetraenoic Acid ◽

Stimulation Of

The present studies were conducted to understand better the regulation of phospholipase A2 (PLA2)-dependent mobilization of lipid mediators by arachidonic acid (C20:4). After stimulation of human neutrophils, g.l.c./m.s. analysis of non-esterified fatty acids indicated that the quantity of C20:4 increased as a function of time after stimulation, from undetectable quantities to > 800 pmol/10(7) cells. In contrast with C20:4, the quantities of other free fatty acids such as oleic and linoleic were high in resting cells and did not change after stimulation. Some 15% of the C20:4 released from cellular lipids remained cell-associated. To examine the effect of C20:4 on its own release, neutrophils were exposed to [2H8]C20:4, to differentiate it by g.l.c./m.s. from naturally occurring C20:4. In A23187-stimulated neutrophils, low concentrations (5-10 microM) of [2H8]C20:4 added just before A23187 increased the quantity of C20:4 produced by the cell, whereas higher concentrations (30-50 microM) decreased the quantity of C20:4 released from phospholipids. As other measures of PLA2 activity, the effects of C20:4 on production of platelet-activity factor (PAF) and leukotriene B4 (LTB4) were assessed. C20:4 treatment just before stimulation of neutrophils blocked PAF and LTB4 production in a concentration-dependent manner (IC50 10-20 microM). The effect of C20:4 was not blocked by the cyclo-oxygenase inhibitor naproxine (10 microM), nor could it be mimicked by 1 microM LTB4, 5-hydroxyeicosa-6,8,11,14-tetraenoic acid (5HETE), 5-hydroperoxyeicosa-6,8,11,14-tetraenoic acid (5HPETE) or 15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15HETE). The 5-lipoxygenase (5LO) inhibitor zileuton induced a concentration-dependent decrease in PAF, with a maximal effect of a 50% decrease at 10-50 microM. The decrease in PAF by the 5LO inhibitor could not be circumvented by addition of 1 microM 5HETE, 5HPETE and LTB4, and may be attributed to the capacity of zileuton to increase the quantity of C20:4 in A23187-treated neutrophils. The inhibitory effect of C20:4 (20-40 microM) on PAF production could be antagonized by the protein kinase C inhibitor staurosporine (30 nM), but not by inhibitors of protein kinase A, tyrosine kinase or calmodulin kinase II. Taken together, these data demonstrate that C20:4 is selectively released from membrane phospholipids of A23187-stimulated neutrophils, and this C20:4 may play an important role in regulating the mobilization of C20:4 by altering PLA2 activity.

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Fluazifop-p-butyl, an aryloxyphenoxypropionate herbicide, diminishes renal and hepatic functions and triggers testicular oxidative stress in orally exposed rats

Toxicology and Industrial Health ◽

10.1177/0748233716657763 ◽

2016 ◽

Vol 33 (5) ◽

pp. 406-415 ◽

Cited By ~ 7

Author(s):

Ayokanmi Ore ◽

Ebenezer Tunde Olayinka

Keyword(s):

Oxidative Stress ◽

Hepatic Function ◽

Dependent Manner ◽

Lactate Dehydrogenase Activity ◽

Group I ◽

Male Wistar Rats ◽

Glutamyl Transferase ◽

The Impact ◽

Dose Dependent ◽

And Oxidative Stress

Fluazifop- p-butyl (FPB) is a selective aryloxyphenoxypropionate herbicide. Its phytotoxicity mechanism involves inhibition of lipid biosynthesis, free-radical generation, and oxidative stress in vulnerable plants. This study evaluates the impact of orally administered FPB on selected tissues in non-target animal model. Twenty-four male wistar rats (160–180g) were randomized into groups (I–IV). Group-I served as control, while animals in groups II, III, and IV received FPB at 18.75, 37.5, and 75 mg/kg body weight/day p.o., respectively, for 21 days. FPB caused significant ( p < 0.05) increase in plasma biomarkers of renal and hepatic function (urea, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) when compared to control. Significant reductions in testicular ascorbic acid, glutathione, and activities of glutathione-S transferase, superoxide dismutase, and catalase were observed in FPB-treated animals when compared to control, in a dose-dependent manner. This was accompanied by increased testicular lipid peroxidation in the treated groups. Furthermore, a significant decrease in testicular acid phosphatase and γ-glutamyl transferase activities was also observed in the FPB-treated groups in a dose-dependent manner compared to control. However, testicular lactate dehydrogenase activity was significantly increased in the FPB-treated rats when compared to control. Additionally, histopathological studies revealed severe interstitial oedema and congestion of testicular blood vessels in the FPB-treated groups. Overall, data from this study suggest that FPB induced hepatotoxicity, nephrotoxicity, and oxidative stress-mediated alteration of testicular functions in rat.

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