Chapter 7 Bacopa Monnieri Deptt. of Med. Elemn. & Toxicology 132 PhD Thesis 7.1. Introduction The marked susceptibility of the kidney to chemical damage has been shown as a function of several contributing factors including its anatomical proximity to blood supply, role in metabolism and excretion of xenobiotics. Hence prevention of renal damage is of great concern. Potassium bromate (KBrO 3 ) is a chemical oxidizing mediator found in drinking water as disinfection by product of surface water ozonation (Kurokawa et al., 1982). Potassium bromate (KBrO 3 ) is widely used as a food additive in the bread- making process for the maturation of flour because of its oxidizing properties and as a neutralizer in cold-wave hair lotions (Kurokawa et al., 1982). It is also used in food products and in the production of fish paste and fermented beverages. It has been shown to produce ROS (Sai et al., 1992), induce lipid peroxidation (Kurokawa, 1990), genotoxicity (Jaloszynski et al., 2007) 8-hydroxyguanosine (8-OH-dG) modification in kidney DNA (Kasai et al., 1987), diminished mitochondrial function and overexpression of glycolytic enzymes (Ahlborn et al., 2009). Nephrotoxicity and neurotoxicity are the primary responses to KBrO 3 with death occurring from solutions containing as little as 12 g KBrO 3 . Although there is no strong evidence available to support the potential carcinogenicity of KBrO 3 to humans, it is classified as a category 2B carcinogen (possibly carcinogenic to humans) based on adequate data of kidney carcinogenicity in rats by the International Agency for Research on Cancer (IARC). Most reports of human toxicity include hearing defects and renal failure following unintentional or purposeful ingestion of few grams of potassium bromate. (De Angelo et al., 1998) Chronic exposures to potassium bromate at drinking water levels above 50 ppm cause renal cell carcinomas in rats, hamsters and mice, and cause thyroid and mesothelioma tumors in rats. It has been demonstrated that KBrO 3 induces renal oxidative stress, renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. KBrO3- has also been reported to mediate generation of oxidative stress (McDorman et al., 2005) which directs augmentation in renal cellular proliferation (Umemura et al., 2004). RCC is the sixth leading cause of cancer deaths in the United States. Scientists reporting the mechanism of potassium bromate-induced toxicity have focused on oxidative stress as a key event in the induction of these carcinomas (McDorman et al., 2005).
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Chapter 7 Bacopa Monnieri
Deptt. of Med. Elemn. & Toxicology 132 PhD Thesis
7.1. Introduction
The marked susceptibility of the kidney to chemical damage has been shown as a
function of several contributing factors including its anatomical proximity to blood
supply, role in metabolism and excretion of xenobiotics. Hence prevention of renal
damage is of great concern. Potassium bromate (KBrO3) is a chemical oxidizing mediator
found in drinking water as disinfection by product of surface water ozonation (Kurokawa
et al., 1982). Potassium bromate (KBrO3) is widely used as a food additive in the bread-
making process for the maturation of flour because of its oxidizing properties and as a
neutralizer in cold-wave hair lotions (Kurokawa et al., 1982). It is also used in food
products and in the production of fish paste and fermented beverages. It has been shown
to produce ROS (Sai et al., 1992), induce lipid peroxidation (Kurokawa, 1990),
genotoxicity (Jaloszynski et al., 2007) 8-hydroxyguanosine (8-OH-dG) modification in
kidney DNA (Kasai et al., 1987), diminished mitochondrial function and overexpression
of glycolytic enzymes (Ahlborn et al., 2009). Nephrotoxicity and neurotoxicity are the
primary responses to KBrO3 with death occurring from solutions containing as little as 12
g KBrO3. Although there is no strong evidence available to support the potential
carcinogenicity of KBrO3 to humans, it is classified as a category 2B carcinogen
(possibly carcinogenic to humans) based on adequate data of kidney carcinogenicity in
rats by the International Agency for Research on Cancer (IARC). Most reports of human
toxicity include hearing defects and renal failure following unintentional or purposeful
ingestion of few grams of potassium bromate. (De Angelo et al., 1998) Chronic
exposures to potassium bromate at drinking water levels above 50 ppm cause renal cell
carcinomas in rats, hamsters and mice, and cause thyroid and mesothelioma tumors in
rats. It has been demonstrated that KBrO3 induces renal oxidative stress, renal cell
tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid.
KBrO3- has also been reported to mediate generation of oxidative stress (McDorman et
al., 2005) which directs augmentation in renal cellular proliferation (Umemura et al.,
2004). RCC is the sixth leading cause of cancer deaths in the United States. Scientists
reporting the mechanism of potassium bromate-induced toxicity have focused on
oxidative stress as a key event in the induction of these carcinomas (McDorman et al.,
2005).
Chapter 7 Bacopa Monnieri
Deptt. of Med. Elemn. & Toxicology 133 PhD Thesis
Bacopa monnieri Linn. (Scrophulariaceae) also known as “Brahmi” is a creeping
glabrous, succulent herb, rooting at nodes, distributed throughout Nepal, china, Taiwan,
Sri Lanka and India in all plain districts, ascending to an altitude of 1,320 m. Its
medicinal efficiency is extensively reported in Indian traditional literature such as Carak
Samhita, Athar-Ved, Susrutu Samhita (Kishore & Singh, 2005) for treatment of epilepsy,
insomnia, anxiety and as a mild sedative and memory enhancer (Ernst, 2006; Tripathi et
al., 1996). As an ayurvedic medicine it is used as a nerve tonic. It is an important
component of south Asian cuisine. It is thought to improve memory, intelligence and
performance of sense organs, and it has also been used to treat asthma (Das et al., 2002).
Besides, B. monnieri (Brahmi) displays antioxidant (Tripathi et al 1996 ; Rajani et al.,
2004) anti-inflammatory, (Channa et al., 2006), antihyperglycemic (Ghosh et al., 2008),
antiamnesic (Prabhakar et al., 2008), antistress (Chowdhuri et al., 2002), and anxiolytic
(Shanker, & Singh 2000) activities too in animals. Bacopa extract contains two prominent
constituents namely, bacoside-A (Singh et al., 1988) and bacoside-B (Basu et al., 1967;
Singh et al., 1988). Herpestien and flavonoids and brahmine are also reported in B.
monnieri (Hou et al., 2002).Bacopa monnieri has been found to be effective against
Nitrobenzene induced liver damage (Menon et al., 2010) and carcinogen induced
hepatotoxicity (Janani et al., 2009). Therefore, we investigated the prophylactic effect of
B. monnieri extract in rats subjected to KBrO3-induced oxidative stress, inflammation,
apoptosis and subsequent renal tumor promotion.
7.2. Results
7.2.1. In vitro results of Bacopa monnieri
Total polyphenolic content of B.monnieri extract was found to be 196 + 0.81 mg GAE/g
(Gallic acid equivalents/g) dry weight. For the measurements of the reducing ability, we
investigated the Fe3+to Fe2+ transformation in the presence of the different concentrations
of extracts using the method of Oyaizu (Oyaizu, 1986). The reducing capacity of a
compound may serve as a significant indicator of its potential antioxidant. In our present
study Reducing potential of B.monnieri increases with increase in absorbance when
compared to control. The addition of Fe2+ or Fe3+ is a common approach to
Chapter 7 Bacopa Monnieri
Deptt. of Med. Elemn. & Toxicology 134 PhD Thesis
experimentally induce oxidative stress in vitro and has also been used in two of our
assays (induction of lipid peroxidation and DNA sugar damage). Data obtained from both
the experiments reveal that there is dose dependent inhibition of Lipid peroxidation and
DNA sugar damage by B.monnieri. DPPH scavenging activity is a specific parameter to
determine the antioxidant activity of plant extracts. B. Monnieri exhibits a significant